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AUTONOMIC NERVOUS SYSTEM Larry J. Ream, Ph.D. Department of Neuroscience, Cell Biology and Physiology 105A White Hall 775-3188 [email protected] READING ASSIGNMENT Preview pages 128-129 in Netter’s and Chapter 6 in Rhoades & Bell. OBJECTIVES • To understand the general organization of the nervous system (central vs. peripheral nervous system) and the role of the autonomic nervous system as an efferent pathway in the peripheral nervous system. • To understand the organization of the autonomic nervous system, specifically in terms of how the sympathetic and parasympathetic nervous systems are organized and which neurotransmitters and receptors they use. • Be able to discuss the general functional roles of the craniosacral vs. the thoracolumbar division of the autonomic nervous system. • To recognize that autonomic function is under control by higher centers in the cortex, limbic system, and hypothalamus. COMPARISON OF SOMATIC AND AUTONOMIC NERVOUS SYSTEMS The peripheral nervous system (PNS) may be subdivided further into a somatic nervous system (SNS), an autonomic nervous system (ANS) and an enteric nervous system (ENS). 703 The ANS, like the SNS, is organized on the basis of a reflex arc. Somatic Nervous System Autonomic Nervous System Dorsal root ganglion IN OUT Spinal nerve Ventral root Primary somatic efferents of the PNS Effector…Skeletal muscle Motoneurons are activated by: Local reflexes; e.g., knee jerk Higher brain centers; e.g., planned, voluntary motor acts Function: Our awareness of the external environment and in directing our skeletal muscle activity to cope with it autonomos self law, governing Primary autonomic efferents of the PNS Function: Govern involuntary functions of the body that do not affect consciousness; e.g., GI tract motility Cardiac activity Contraction of the urinary bladder Constriction of the iris of the eye Effectors include… Smooth muscle Cardiac muscle Glands …but not skeletal muscle autonomic autonomic 704 • The SNS consists of (1) sensory neurons that convey information from somatic receptors in the head, body wall, and limbs and from receptors for special senses of vision, hearing, taste, and smell (exteroceptors and proprioceptors) to the CNS and (2) motor neurons that conduct impulses from the CNS to skeletal muscles only. Because these motor responses can be consciously controlled, the action of this part of the PNS is voluntary. > Each of its efferent pathways consists of a single motoneuron and the skeletal muscle fibers it innervates. When a somatic motoneuron stimulates a skeletal muscle, the muscle contracts; the effect is always excitation. > The soma of the motoneuron is located in either the brainstem or spinal cord, and its axon synapses directly on skeletal muscle. Acetylcholine is released from presynaptic terminals of the motoneurons and activates nicotinic receptors located on the motor end plates of the skeletal muscle. GSE excitation ACh A α-motoneuron GENERAL PLAN: GSA R exteroceptor or proprioceptor e.g., muscle spindle naked nerve ending Meissnerʼs corpuscle Golgi tendon organ GSE CNS E monosynaptic or polysynaptic SPINAL CORD skeletal muscle BRAINSTEM Spinal nerves GSE Cranial nerves GSE 705 • The ANS consists of (1) sensory neurons that convey information from autonomic sensory receptors, located primarily in visceral organs to the CNS, and (2) motor neurons that conduct nerve impulses from the CNS to smooth muscle, cardiac muscle, and glands. Because its motor responses are not normally under conscious control, the action of the ANS is involuntary. > Autonomic sensory neurons are associated with interoceptors, such as chemoreceptors that monitor blood CO2 level and mechanoreceptors that detect the stretch in the walls of organs or blood vessels. These sensory signals are not consciously perceived most of the time, although intense activation of interoceptors may produce conscious sensations. Three examples of visceral sensations that are perceived are sensations of pain from damaged viscera, angina pectoris (chest pain) from inadequate blood flow to the heart, and fullness of the urinary bladder. > Each efferent pathway consists of two neurons: a preganglionic and a postganglionic neuron. > The soma of the preganglionic neuron is located in the CNS. Axons from these neurons synapse on the soma of postganglionic neurons in one of several autonomic ganglia. > The axons of postganglionic neurons then travel to the periphery, where they synapse on visceral effector organs. > All preganglionic neurons release acetylcholine. Postganglionic neurons release either acetylcholine or norepinephrine, or, in some cases, neuropeptides. GVE excitation or inhibition 1 ACh or NE 2 B C GENERAL PLAN: GVA R interoceptor SPINAL CORD GVE…two neurons in series CNS E neuron 1 BRAINSTEM Cranial nerves GVE Spinal nerves GVE 706 neuron 2 Summary of Somatic and Autonomic Nervous Systems Characteristic Sensory input Control of motor output Motor neuron pathway Somatic Nervous System Special senses and somatic senses. Voluntary control from cerebral cortex, with contributions from basal ganglia, cerebellum, brainstem, and spinal cord. One-neuron pathway: Somatic motoneurons extending from CNS synapse directly with effector. Neurotransmitters and hormones All somatic motoneurons release ACh. Effectors Skeletal muscle. Responses Contraction of skeletal muscle. 707 Autonomic Nervous System Mainly from interoceptors; some from special senses. Involuntary control from limbic system, hypothalamus, brainstem, and spinal cord; limited control from cerebral cortex. Usually two-neuron pathway: Preganglionic neurons extending from CNS synapse with postganglionic neurons in an autonomic ganglion, and postganglionic neurons extending from ganglion synapse with a visceral effector. Alternatively, preganglionic neurons may extend from CNS to synapse with cells of the adrenal medullae. All preganglionic axons release ACh; most sympathetic postganglionic neurons release NE; those to most sweat glands release ACh; all parasympathetic postganglionic neurons release ACh; adrenal medullae release epinephrine and NE. Smooth muscle, cardiac muscle, and glands. Visceral effector organs such as the heart, bronchioles, vascular smooth muscle, GI tract, bladder, and genitalia. Contraction or relaxation of smooth muscle; increased or decreased rate and force of contraction of cardiac muscle; increased or decreased secretions of glands. ORGANIZATION AND GENERAL FEATURES OF THE ANS • The motor part of the ANS consists of two branches, the sympathetic division and the parasympathetic division. • With a few exceptions, effectors receive nerves from both divisions, and usually the two divisions have opposing actions, i.e., act reciprocally in their effect on end organs. > For example, cardiovascular activity: SNS stimulation ➔ ↑HR, ↑SV (↑HR x ↑SV = ↑CO) PNS stimulation ➔ ↓HR, ↓SV (↓HR x ↓SV = ↓CO) > Not true for all organs, however. For example, sweat glands and limb vasculature only receive sympathetic innervation. • A third division of the ANS, the enteric nervous system, is located in plexuses of the gastrointestinal tract. VARIATIONS: P S long short P S short long ACh neuron 1 P S ACh or NE neuron 2 synapse preganglionic P: cell body in nucleus in brainstem or spinal cord S: cell body in spinal cord only postganglionic cell body in ganglion synapse 708 smooth muscle heart gland excitation or inhibition EXCEPTIONS: 1. sympathetics to adrenal medullae: ACh adrenal medulla preganglionic sympathetic general plan — sympathetics to eccrine sweat glands: NE hands and feet preganglionic sympathetic postganglionic sympathetic 2. sympathetics to most sweat glands: ACh preganglionic sympathetic postganglionic sympathetic most body regions thermoregulatory sweat glands 709 Organization of the Autonomic Nervous System Characteristic Origin of preganglionic neurons Location of autonomic ganglia Length of preganglionic axons Length of postganglionic axons Neuroeffector junctions Neurotransmitter and receptor type in ganglion Neurotransmitter in effector organs Receptor types in effector organs Sympathetic Division Spinal cord segments T1-L2 (thoracolumbar) Paravertebral and prevertebral Short Parasympathetic Division Nuclei of CN III, VII, IX and X; spinal cord segments S2-S4 (craniosacral) In or near effector organs Long Somatic Nervous System Long Short Diffuse, branching; receptors not concentrated in one region ACh/nicotinic receptor Diffuse, branching; receptors not concentrated in one region ACh/ nicotinic receptor Discrete, organized; ACh receptors localized on motor end plate NE (except for most sweat glands) α1, α2, β1, β2 ACh ACh Muscarinic Nicotinic Somatic Nicotinic receptor Sympathetic Nicotinic receptor α 1, α 2, β 1, β 2 receptors Nicotinic receptor Muscarinic receptor Parasympathetic Adrenal Nicotinic receptor 710 ANATOMICAL COMPONENTS OF AUTONOMIC MOTOR PATHWAYS Preganglionic neurons (myelinated, type B) 1. Sympathetic division Thoracolumbar outflow (T1-L2) Preganglionic cell bodies are located at thoracic levels 1 through 12 and lumbar 1 through 2 (or 3)…in the intermediolateral cell column of spinal cord Short fibers in the white rami Synapse in paravertebral (chain) ganglia… OR synapse in prevertebral ganglia via splanchnic nerves • Celiac ganglion → stomach, spleen, liver and kidney • Superior mesenteric ganglion → small intestine and colon • Inferior mesenteric ganglion → colon, rectum, bladder, genital organs Note: All three supply the enteric nervous system of the GI tract 711 2. Parasympathetic division Craniosacral outflow (CN III, VII, IX, X [80%], S2-S4) Preganglionic neurons are located in brainstem cranial nerve nuclei and the sacral spinal cord levels 2 through 4 Long preganglionic fibers Synapse in terminal ganglia…two types: • cranial nerve head ganglia: • intramural ganglia: MEDULLA → Dorsal motor nucleus of the vagus n. (X) 712 Postganglionic neurons (unmyelinated, type C) 1. Sympathetic division Long postganglionic fibers in the gray rami One preganglionic fiber → 20+ postganglionic fibers Extensive branching of both pre- and postganglionic neurons Divergence…sympathetic responses tend to be widespread throughout the body 2. Parasympathetic division Short postganglionic fibers One preganglionic fiber → 4-5 postganglionic fibers Parasympathetic effects tend to be localized Exception: Preganglionic sympathetic fibers to adrenal medullae LONG LONG 713 SYMPATHETIC GANGLIA Sympathetic ganglia lie in two chains on either side of the vertebral column (sympathetic chain ganglia) and near large abdominal arteries anterior to the vertebral column (prevertebral ganglia). White ramus…contains myelinated, type B axons Gray ramus…contains unmyelinated, type C axons Gray rami outnumber the white rami… • only thoracic and first two or three lumbar nerves have white rami • gray rami lead to each of the 31 pairs of spinal nerves 714 AUTONOMIC MOTOR PATHWAYS: STRUCTURE OF THE SYMPATHETIC DIVISION Thoracolumbar outflow Cell bodies of sympathetic preganglionic neurons are located in the lateral horns of gray matter in the 12 thoracic and first two (and sometimes three) lumbar segments of the spinal cord. 715 AUTONOMIC MOTOR PATHWAYS: STRUCTURE OF THE PARASYMPATHETIC DIVISION Craniosacral outflow Cell bodies of parasympathetic preganglionic neurons are located in brainstem nuclei and in the lateral horns of gray matter in the second through fourth sacral segments of the spinal cord. 716 AUTONOMIC PLEXUSES • In the thorax, abdomen, and pelvis, axons of both sympathetic and parasympathetic neurons form tangled networks of autonomic plexuses, many of which lie along major arteries. These plexuses also may contain sympathetic ganglia and axons of autonomic sensory neurons. • The major plexuses in the thorax are the cardiac plexus, which supplies the heart, and the pulmonary plexus, which supplies the bronchial tree. • The abdomen and pelvis also contain major autonomic plexuses and often the plexuses are named after the artery along which they are distributed. The celiac (solar) plexus is the largest autonomic plexus and surrounds the celiac and superior mesenteric arteries. It contains two large celiac ganglia and a dense network of autonomic axons and is distributed to the liver, gallbladder, stomach, pancreas, spleen, kidneys, adrenal medullae, testes, and ovaries. • Other important autonomic plexuses are the superior mesenteric plexus, inferior mesenteric plexus, the hypogastric plexus, and the renal plexuses. ANS NEUROTRANSMITTERS • Based on the neurotransmitter they produce and release, autonomic neurons are classified as either cholinergic or adrenergic. • Cholinergic neurons release acetylcholine; receptors for ACh are called cholinoreceptors. (Note: A third term is non-adrenergic, non-cholinergic, which describes some postganglionic parasympathetic neurons of the GI tract that release peptides, e.g., substance P, or other substances, e.g., nitric oxide, as their neurotransmitter.) In the ANS, cholinergic neurons include: - all sympathetic and parasympathetic preganglionic neurons, - sympathetic postganglionic neurons that innervate most sweat glands, and - all parasympathetic postganglionic neurons. • Adrenergic neurons release norepinephrine; receptors for NE on the effector organs are adrenoreceptors. (Note: Adrenoreceptors may also be activated by epinephrine from the adrenal medulla.) Most sympathetic postganglionic neurons are adrenergic. NEUROEFFECTOR JUNCTIONS OF THE ANS • In contrast to the SNS, in the ANS, the postganglionic neurons that innervate target tissues form diffuse, branching networks. Varicosities line these branches and are the sites of neurotransmitter synthesis, storage, and release. (The varicosities are analogous to the presynaptic nerve terminals of the neuromuscular junction in the SNS.) • There is overlap in the branching networks from different postganglionic neurons, such that target tissues may be innervated by many postganglionic neurons. • Postganglionic receptors are widely distributed on the target tissues, and there is no specialized region of receptors analogous to the motor end plate of skeletal muscle. 717 CHOLINORECEPTORS • The two types of cholinergic receptors, both of which bind ACh, are nicotinic receptors and muscarinic receptors. • Nicotinic receptors are present in the plasma membrane of dendrites and cell bodies of both sympathetic and parasympathetic postganglionic neurons (i.e., in the autonomic ganglia), in the motor end plate at the neuromuscular junction, and in the adrenal medulla. α 1, α 2, β 1, β 2 Sympathetic Smooth muscle, glands Parasympathetic Motoneuron Skeletal muscle Preganglionic Adrenal medulla Somatic Adrenal medulla • Nicotinic receptors produce excitation, and they are blocked by ganglionic blockers (e.g., hexamethonium) in the autonomic ganglia, but not at the neuromuscular junction. • Mechanism of action: ACh binds to the α subunits of the nicotinic ACh receptor. The nicotinic ACh receptors are also ion channels for Na+ and K+. IONOTROPIC RECEPTORS i.e., chemically-gated ion channels 718 • Muscarinic receptors are present in the plasma membrane of all effectors (smooth muscle, cardiac muscle, and glands) innervated by parasympathetic postganglionic axons. • Most sweat glands receive their innervation from cholinergic sympathetic postganglionic neurons and possess muscarinic receptors. …all but hands and feet • Activation of nicotinic receptors by ACh causes depolarization and thus excitation of the postsynaptic cell…either a postganglionic neuron, an autonomic effector in smooth muscle and glands), or a skeletal muscle fiber. • Activation of muscarinic receptors by ACh sometimes causes depolarization and sometimes causes hyperpolarization, depending on which particular cell bears the muscarinic receptors. > For example, binding of ACh to muscarinic receptors inhibits (relaxes) smooth muscle sphincters in the GI tract. > By contrast, ACh excites smooth muscle fibers in the circular muscles of the iris of the eye, causing them to contract. • Note: Because ACh is quickly inactivated by acetylcholinesterase, effects triggered by cholinergic neurons are brief. • Muscarinic receptors are blocked by atropine. • Mechanism of action: > Heart SA node. Inhibition of adenylate cyclase, which leads to the opening of K+ channels, slowing the rate of spontaneous Phase 4 depolarization, and decreased heart rate. > Smooth muscle and glands. Formation of IP3 and increase in intracellular Ca++. METABOTROPIC RECEPTORS i.e., elicits 2nd-messenger cascades 719 ADRENORECEPTORS • Adrenergic receptors bind both NE (both neurotransmitter and hormone) and epinephrine (hormone). • The two main types of adrenoreceptors are alpha (α) receptors and beta (β) receptors, which are found on visceral effectors innervated by most sympathetic postganglionic axons. • These receptors are further classified into subtypes—α 1, α 2, β 1, β 2—based on the specific responses they elicit and by their selective binding of drugs that activate or block them. Although there are some exceptions… > activation of α1 and β1 receptors generally produces excitation, whereas > activation of α2, and β2 receptors causes inhibition of effector tissues. • β3 receptors are present only on cells of brown adipose tissue, where their activation causes thermogenesis. • Cells of most effectors contain either alpha or beta receptors; some visceral effector cells contain both. NE stimulates alpha receptors more strongly than beta receptors, whereas epinephrine is a potent stimulator of both alpha and beta receptors. • The activity of NE at a synapse is terminated when the NE is taken up by the axon that released it or when the NE is inactivated by catechol-O-methyltransferase (COMT) or monoamine oxidase (MAO). Compared to ACh, NE lingers in the synaptic cleft for a longer time. Thus, effects triggered by adrenergic neurons typically are longer than those triggered by cholinergic neurons. • Mechanisms of action: Receptor α1 α2 Location On vascular smooth muscle of the skin and splanchnic regions, GI and bladder sphincters, and the radial muscle of the iris In presynaptic nerve terminals, platelets, fat cells, walls of the GI tract β1 In the SA node, AV node, and ventricular muscle of the heart β2 On vascular smooth muscle of skeletal muscles, bronchial smooth muscle, and in the walls of the GI tract and bladder Mechanism of Action Formation of IP3 and increase in intracellular Ca++ Inhibition of adenylate cyclase and decrease in cAMP Activation of adenylate cyclase and increase in cAMP Activation of adenylate cyclase and increase in cAMP METABOTROPIC RECEPTORS i.e., elicits 2nd-messenger cascades 720 Locations and Responses of Adrenergic and Cholinergic Receptors Receptor Cholinergic Major Locations Integral proteins in postsynaptic plasma membranes; activated by ACh Effects of Receptor Activation Nicotinic Plasma membrane of postganglionic sympathetic and parasympathetic neurons Excitation → impulses in postganglionic neurons Chromaffin cells of adrenal medullae Epinephrine and NE secretion Motor end plate of skeletal muscle Excitation → contraction Effectors innervated by parasympathetic postganglionic neurons In some receptors, excitation; in others, inhibition Sweat glands innervated by cholinergic sympathetic postganglionic neurons Increased sweating Skeletal muscle blood vessels innervated by cholinergic postganglionic sympathetic fibers Integral proteins in postsynaptic plasma membranes; activated by the neurotransmitter epinephrine, and by hormonal NE and epinephrine Inhibition → relaxation → vasodilation Smooth muscle fibers in blood vessels that serve salivary glands, skin, mucosal membranes, kidneys, and abdominal viscera; radial muscle in iris of eye; sphincter muscles of stomach and urinary bladder Excitation → contraction, which causes vasoconstriction, dilation of pupil, and closing of sphincters Salivary gland cells Secretion of K+ and water Sweat glands on palms and soles Increased sweating Smooth muscle fibers in some blood vessels Inhibition → relaxation → vasodilation Beta cells of pancreatic islets that secrete insulin Decreased insulin secretion Pancreatic acinar cells Inhibition of digestive enzyme secretion Platelets in blood Aggregation to form platelet plug Muscarinic Adrenergic α1 α2 β1 Cardiac muscle fibers Excitation → increased force and rate of contraction Juxtaglomerular cells of kidneys Renin secretion Posterior pituitary Secretion of ADH Adipocytes β2 Breakdown of triglycerides → release of fatty acids into blood Smooth muscle in walls of airways; in blood vessels that serve the heart, skeletal muscle, adipose tissue, and liver; and in walls of visceral organs, such as urinary bladder Hepatocytes in liver β3 Inhibition → relaxation, which causes dilation of airways, vasodilation, and relaxation of organ walls Glycogenolysis Brown adipose tissue Thermogenesis 721 Effects of Sympathetic and Parasympathetic Divisions on Blood Vessels Vascular smooth muscle Salivary gland arterioles Gastric gland arterioles Intestinal gland arterioles Coronary arterioles Skin and mucosal arterioles Skeletal muscle arterioles Abdominal viscera arterioles Brain arterioles Kidney arterioles Systemic veins Effect of Sympathetic Stimulation (α or β adrenergic receptors, except as noted) Vasoconstriction, which decreases secretion (α1) Vasoconstriction, which inhibits secretion (α1) Vasoconstriction, which inhibits secretion (α1) Relaxation → vasodilation (β2) Contraction → vasoconstriction (α1, α 2) Contraction → vasoconstriction (muscarinic ACh receptors) Constriction: vasoconstriction (α1) Contraction → vasoconstriction (α1) Relaxation → vasodilation (β2) Relaxation → vasodilation (muscarinic ACh receptors) Contraction → vasoconstriction (α1, β 2) Slight contraction → vasoconstriction (α1) Constriction of blood vessels → decreased urine volume (α1) Contraction → constriction (α1) Relaxation → dilation (β2) 722 Effect of Parasympathetic Stimulation (muscarinic ACh receptors) Vasodilation, which increases K+ and water secretion Secretion of gastric juice Secretion of intestinal juice Contraction → vasoconstriction Vasodilation, which may not be physiologically significant Drugs that Affect Autonomic Activity Type of Receptor Adrenergic α1 Agonist Antagonist Norepinephrine Phenylephrine (NeoSynephrine) Phenoxybenzamine Phentolamine Prazosin (Minipress) α2 Clonidine Yohimbine β1 Norepinephrine Isoproterenol (Isuprel) Dobutamine Propranolol Metoprolol β2 Isoproterenol (Isuprel) Albuterol Propranolol (Inderal) Butoxamine Acetylcholine Nicotine Carbachol Curare Hexamethonium (ganglion, Cholinergic Nicotinic Muscarinic Acetylcholine Muscarine Carbachol but not neuromuscular junction) Atropine NE Beta2 Beta-blocker drug Most sympathetic pathways Beta1 Alpha Alpha-blocker drug 723 SYMPATHETIC ADRENERGIC VARICOSITIES • Sympathetic adrenergic varicosities contain both the classic neurotransmitter (NE) and non-classic neurotransmitters (ATP and neuropeptide Y). • The classic neurotransmitter, norepinephrine, is synthesized from tyrosine in the varicosities and stored in small dense-core vesicles, ready for release; these small densecore vesicles also contain dopamine β-hydroxylase, which catalyzes the conversion of dopamine to NE (the final step in the synthetic pathway), and ATP. • A separate group of large dense-core vesicles contain neuropeptide Y. Small dense-core vesicle Clear vesicle Large dense-core vesicle PARASYMPATHETIC CHOLINERGIC VARICOSITIES • The parasympathetic cholinergic varicosities release both the classic neurotransmitter —ACh—and non-classic neurotransmitters—e.g., vasoactive intestinal peptide (VIP) and nitric oxide (NO). • The classic neurotransmitter, acetylcholine, is synthesized in the varicosities from choline and acetyl CoA and stored in small clear vesicles. A separate group of large dense-core vesicles contain peptides such as VIP. The varicosities also contain nitric oxide synthase and can synthesize NO on demand. 724 SYMPATHETIC VS. PARASYMPATHETIC RESPONSES • Most body organs receive innervation from both divisions of the ANS, which typically work in opposition to one another. • The balance between sympathetic and parasympathetic activity or “tone” is regulated by the HYPOTHALAMUS. • A few structures receive only sympathetic innervation—sweat glands, arrector pili muscles, the kidneys, the spleen, most blood vessels, and the adrenal medullae. Sympathetic During physical or emotional stress, the sympathetic division dominates over the parasympathetic system Fight-or-flight response…prepares the body for emergency situations…expenditure of energy [Along with hormones from the adrenal medullae] “four E situations” Exercise Emergency Excitement Embarrassment Includes increased heart rate, cardiac output and blood pressure; redistribution of blood flow away from skin and splanchnic regions and toward active muscles; increased metabolic rate; increased blood glucose concentration; increased ventilation, with dilation of the airways; decreased GI motility and secretions; and increased mental activity More widespread and longer lasting than parasympathetic responses: • divergence is more extensive; as a result, many tissues are activated simultaneously • slower break down of NE compared to ACh • NE (and epinephrine) also from adrenal medullae Parasympathetic The parasympathetic division enhances “rest-and-digest” activities Energy conservation-restorative system…conserve and restore body energy during times of rest or recovery “SLUDD” Salivation Lacrimation Urination Digestion Defecation Also “three decreases” - decreased heart rate - decreased airway diameter (bronchoconstriction) - decreased pupil diameter (pupillary constriction) 725 Effects of the ANS on Organ Systems Sympathetic receptor β1 β1 β1 Parasympathetic Action* ↓ heart rate ↓ contractility (atria) ↓AV node conduction Organ Heart Sympathetic Action ↑ heart rate ↑ contractility ↑ AV node conduction Vascular smooth muscle Constricts blood vessels in skin; splanchnic Dilates blood vessels in skeletal muscle α1 GI tract ↓ motility Constricts sphincters α2, β2 α1 ↑ motility Relaxes sphincters Bronchioles Dilates bronchiolar smooth muscle β2 Constricts bronchiolar smooth muscle Male sex organs Ejaculation α Erection Bladder Relaxes bladder wall Constricts sphincter β2 α1 Contracts bladder wall Relaxes sphincter Sweat glands ↑ sweating Muscarinic** Kidney ↑ renin secretion β1 Adipocytes ↑ lipolysis β1 *Receptors are muscarinic ** Sympathetic cholinergic 726 β2 HYPOTHALAMIC AND BRAINSTEM CENTERS • Centers in the hypothalamus and brainstem coordinate the autonomic regulation of organ system functions. • Axons extend from the hypothalamus to sympathetic and parasympathetic nuclei in the brainstem and spinal cord. • Through the ANS, the hypothalamus is a major regulator of visceral activities, including temperature regulation, thirst, food intake (satiety), micturition, breathing, and cardiovascular (vasomotor) activity. • The medulla contains several nuclei that control vital body functions. The cardiovascular center regulates the rates and the force of the heartbeat and the diameter of blood vessels. The medullary rhythmicity area of the respiratory center adjusts the basic rhythm of breathing. Other nuclei in the medulla control reflexes for vomiting, coughing, swallowing, hiccupping, and sneezing. • The pons contains the pneumotaxic and the apneustic areas. Together with the medullary rhythmicity area, these areas help control breathing. 727 Autonomic Regulation of Heart Rate INPUT TO CARDIOVASCULAR CENTER From higher brain centers: cerebral cortex, limbic system, and hypothalamus From sensory receptors: Proprioceptors—monitor joint movements + Chemoreceptors—monitor blood H , CO2, O2 Baroreceptors—monitor blood pressure OUTPUT TO HEART Increased rate of spontaneous depolarization in SA node (and AV node) increases heart rate Cardiovascular center Increased contractility of atria and ventricles increases stroke volume Decreased rate of spontaneous depolarization in SA node (and AV node) decreases heart rate 1. Cardiac accelerator nerves (sympathetic) 2. Vagus (X) nerves (parasympathetic) • Even before physical activity begins, especially in competitive situations, heart rate may climb. This anticipatory increase occurs because the limbic system sends nerve impulses to the CV center. As physical activity begins, proprioceptors that are monitoring the position of the limbs and muscles send nerve impulses at an increased frequency to the CV center. Proprioceptor input is a major stimulus for the quick rise in heart rate that occurs at the onset of physical activity. • Other sensory receptors that provide input to the CV center include chemoreceptors, which monitor the chemical changes in the blood, and baroreceptors, which monitor the stretching of major arteries and veins caused by the pressure of the blood flowing through them. Important baroreceptors are the carotid sinus and the aortic sinus, which detect changes in blood pressure and provide input to the CV center when it changes. The vasomotor center compares this information to a blood pressure set point. If corrections are necessary, the vasomotor center orchestrates changes in output of both the sympathetic and the parasympathetic innervation of the heart and blood vessels to bring about the necessary change in blood pressure. • Sympathetic neurons extend from the medulla into the spinal cord. From the thoracic region of the spinal cord, sympathetic cardiac accelerator nerves extend out to the SA node, AV node, and most portions of the myocardium. Impulses in these nerves trigger the release of NE, which binds to β1 receptors on cardiac muscle fibers. This interaction has two specific effects: (1) In SA (and AV) node fibers, NE speeds the rate of spontaneous depolarization so that these pacemakers fire impulses more rapidly and heart rate increases; (2) in contractile fibers throughout the atria and ventricles, NE enhances 728 Ca++ entry through voltage-gated slow Ca++ channels, thereby increasing contractility. As a result, a greater volume of blood is ejected during systole. With a moderate increase in heart rate, SV does not decline because the increased contractility offsets the decreased preload. With maximal sympathetic stimulation, however, heart rate may reach 200 beats/min in a 20-year-old person. At such a high heart rate, SV is lower than at rest due to the very short filling time. The maximal heart rate declines with age; as a rule, subtracting one’s age from 220 provides a good estimate of maximal heart rate in beats per minute. • Parasympathetic nerve impulses reach the heart via the right and left vagus (X) nerves. Vagal axons terminate in the SA node, AV node, and atrial myocardium. They release ACh, which decreases heart rate by slowing the rate of spontaneous depolarization in autorhythmic fibers. As only a few vagal fibers innervate ventricular muscle, changes in parasympathetic activity have little effect on the contractility of the ventricles. • A continually shifting balance exists between sympathetic and parasympathetic stimulation of the heart. At rest, parasympathetic stimulation predominates. The resting heart rate—about 75 beats per minute—is usually lower than the autorhythmic rate of the SA node (~100 beats per minute). With maximal stimulation by the parasympathetic division, the heart can slow to 20 or 30 beats/min., or can even stop momentarily. REVIEW QUESTIONS 1. The ANS innervates all of the following EXCEPT A. muscles in the wall of the stomach B. biceps muscle C. cardiac muscle D. pituitary gland 729 E. muscles responsible for vasoconstriction 2. Cell bodies of preganglionic sympathetic neurons are located A. in the brain B. in the sacral spinal cord C. in the thoracic spinal cord D. throughout the CNS E. in autonomic ganglia only 3. Which autonomic receptor is activated by low concentrations of epinephrine released from the adrenal medulla and causes vasodilation? A. Adrenergic α receptors B. Adrenergic β1 receptors C. Adrenergic β2 receptors D. Cholinergic muscarinic receptors E. Cholinergic nicotinic receptors 4. Which of the following autonomic drugs acts by stimulating adenylate cyclase? A. Atropine B. Clonidine C. Curare D. Norepinephrine E. Propranolol 5. Which autonomic receptor mediates secretion of epinephrine by the adrenal medulla? A. Adrenergic α receptors B. Adrenergic β1 receptors C. Adrenergic β2 receptors D. Cholinergic muscarinic receptors E. Cholinergic nicotinic receptors 6. Which autonomic receptor mediates an increase in heart rate? A. Adrenergic α receptors B. Adrenergic β1 receptors C. Adrenergic β2 receptors D. Cholinergic muscarinic receptors E. Cholinergic nicotinic receptors 7. Which adrenergic receptor produces its stimulatory effects by the formation of IP3 and an increase in intracellular Ca++? A. α1 receptors B. α2 receptors C. β1 receptors D. β2 receptors E. Muscarinic receptors 8. Which of the following responses is mediated by parasympathetic muscarinic responses? A. Dilation of bronchiolar smooth muscle B. Erection C. Ejaculation D. Constriction of GI sphincters E. Increased cardiac contractility 730 9. Which autonomic receptor is blocked by hexamethonium at the ganglia, but not at the neuromuscular junction? A. Adrenergic α receptors B. Adrenergic β1 receptors C. Adrenergic β2 receptors D. Cholinergic muscarinic receptors E. Cholinergic nicotinic receptors 10. NE and epinephrine both increase the heart rate and produce vasoconstriction in the skin. On the other hand, epinephrine produces vasodilation in skeletal muscle where NE produces vasoconstriction. These observations are consistent with the view that A. NE stimulates only α receptors B. NE stimulates only β receptors C. NE stimulates α receptors of the heart and β receptors of the arterioles D. NE stimulates α receptors of arterioles and β receptors of the heart, but not β receptors of the arterioles E. epinephrine stimulates only β receptors 11. Atropine is a drug that blocks the action of ACh on smooth muscles, glands, and the heart. Which of the following actions would you expect atropine to have? A. loss of control over the diaphragm B. Cardiac asystole C. Pupillary constriction D, Decreased bronchial secretions 12. Which of the following is a feature of the sympathetic, but not the parasympathetic, nervous system? A. Ganglia located in the effector organs B. Long preganglionic fibers C. Preganglionic neurons release NE D. Preganglionic neurons release ACh E. Preganglionic neurons originate in the thoracolumbar spinal cord F. Postganglionic neurons synapse on effector organs G. Postganglionic neurons release epinephrine H. Postganglionic neurons release ACh 13. The only action below not caused by stimulation of postganglionic sympathetic neurons is A. an increase in heart rate and stroke volume B. vasodilation in the gastrocnemius muscle C. erection of the penis D. ejaculation in the male E. renin secretion 14. The only action below not caused by stimulation of postganglionic parasympathetic neurons is A. release of ACh B. a decreased conduction time in the AV node of the heart C. relaxation of the internal anal sphincter D. contraction of the circular muscle of the iris E. secretion by the sweat glands 731 15. What type of receptor does epinephrine stimulate in veins to produce venous constriction? A. Nicotinic B. Muscarinic C. α1 D. α2 E. β1 16. What type of receptor does epinephrine stimulate in the arterioles to produce arteriolar constriction? A. Nicotinic B. Muscarinic C. α1 D. α2 E. β1 17. What type of receptor does epinephrine stimulate in arterioles to decrease arteriolar constriction? A. Nicotinic B. Muscarinic C. α2 D. β1 E. β2 18. Terminal ganglia are where A. the cell bodies for sympathetic preganglionic fibers are located. B. preganglionic parasympathetic fibers synapse with postganglionic parasympathetic fibers. C. the cell bodies of sensory neurons are located. D. preganglionic sympathetic fibers synapse with postganglionic sympathetic fibers. E. preganglionic sympathetic fibers synapse with postganglionic parasympathetic fibers. 19. Most autonomic sensory neurons are associated with A. exteroceptors B. interoceptors C. proprioceptors D. special senses E. somatic efferent neurons 20. To say that most organs served by the ANS have “dual innervation” means that A. these organs release either ACh or NE when stimulated. B. it takes two postganglionic neurons to achieve the desired response. C. the organs are innervated by both sympathetic and parasympathetic neurons. D. the organs have both α and β receptors. E. both a preganglionic and postganglionic neuron go to the organ. 21. An adrenergic neuron produces the neurotransmitter A. serotonin. B. GABA. C. NE. D. ACh. E. glycine. 732 22. The term “craniosacral outflow” refers to A. release of ACh from preganglionic neurons. B. axons of postganglionic parasympathetic neurons. C. axons of postganglionic sympathetic neurons. D. axons of preganglionic parasympathetic neurons. E. axons of preganglionic sympathetic neurons. 23. In which of the following would synapses between preganglionic and postganglionic sympathetic fibers occur? A. Ciliary ganglion B. Superior mesenteric ganglion C. Celiac ganglion D. Otic ganglion 24. Which of the following responses is initiated by the sympathetic nervous system? A. Decreased heart rate B. Constriction of the pupils C. Splitting glycogen to glucose by the liver D. Constriction of the bronchioles E. Decreased blood pressure 25. Parasympathetic stimulation to the nasal mucosa, pharynx, and lacrimal glands is provided by fibers arising from the A. superior cervical ganglion. B. middle cervical ganglion. C. inferior cervical ganglion. D. sphenopalatine ganglion. E. submandibular ganglion. 26. A major organ that receives sympathetic stimulation, but not parasympathetic stimulation is the A. heart. B. liver. C. stomach. D. lung. E. kidney. 27. ACh exerts its effects on postsynaptic cells when it A. is broken down by enzymes in the synaptic cleft, and the end-products diffuse into the postsynaptic cell. B. binds to specific receptors on the postsynaptic cell membrane and changes the permeability of the membrane to particular ions. C. diffuses into the postsynaptic cell and changes the pH of the intracellular fluid. D. actively transports ions from the synaptic cleft into the postsynaptic cell. E. blocks specific receptors to which other neurotransmitters could attach. 28. Because the principal active ingredient in tobacco is nicotene, you might expect smoking to enhance the effects of A. ACh of parasympathetic visceral effectors. B. ACh on any postganglionic neurons. C. NE on the heart and blood vessels. D. NE on most sympathetic visceral effectors. 733 29. Cholinergic postganglionic sympathetic neurons stimulate the A. adrenal medullae. B. heart. C. sweat glands. D. walls of the GI tract. 30. You have just discovered that your pants were unzipped the entire time you gave a speech to your small group session in our CaTOS class. Which of the following responses would you likely experience? A. Increased parasympathetic stimulation to the iris. B. Increased parasympathetic stimulation to the stomach. C. Increased sympathetic stimulation to the heart. D. Decreased sympathetic stimulation to the bronchioles. E. Decreased sympathetic stimulation to the small intestine. 31. Which of the following is stimulated by the parasympathetic nervous system? A. Dilation of the bronchioles B. Erection of the penis D. Dilation of the pupil D. Increased secretion by sweat glands in the palms and soles 32. You are just about to perform a certain “sensitive” clinical procedure for the first time on a real patient in your ICM class and your palms begin to sweat. This is due to A. increased sympathetic stimulation of sweat glands possessing α receptors. B. increased sympathetic stimulation of sweat glands possessing β receptors. C. increased parasympathetic stimulation of sweat glands possessing nicotinic receptors. D. increased parasympathetic stimulation of sweat glands possessing muscarinic receptors. E. increased sympathetic stimulation of sweat glands possessing muscarinic receptors. F. an allergic reaction to latex gloves. 33. A patient with chronic hypertension is treated with prazosin by his physician. The treatment successfully decreases the patient’s blood pressure to within the normal range. What is the mechanism of the drug’s action? A. Inhibition of β1 receptors in the SA node B. Inhibition of β2 receptors in the SA node C. Stimulation of muscarinic receptors in the SA node D. Stimulation of nicotinic receptors in the SA node E. Inhibition of β1 receptors in ventricular muscle F. Stimulation of β1 receptors in ventricular muscle G. Inhibition of α1 receptors in ventricular muscle H. Stimulation of α1 receptors in the SA node I. Inhibition of α1 receptors in the SA node J. Inhibition of α1 receptors on vascular smooth muscle K. Stimulation of α1 receptors on vascular smooth muscle L. Stimulation of α2 receptors on vascular smooth muscle 34. Prevertebral ganglia receive preganglionic parasympathetic fibers. A. True B. False 734 35. Axons of preganglionic parasympathetic neurons synapse with 20 or more postganglionic neurons. A. True B. False 36. Cholinergic neurons release NE and epinephrine. A. True B. False 37. All preganglionic neurons release ACh. A. True B. False 38. Nicotinic receptors bind epinephrine. A. True B. False 39. Atropine is a drug that blocks muscarinic receptors. A. True B. False 40. Monoamine oxidase inactivates epinephrine (and NE). A. True B. False 41. Activation of β3 receptors causes thermogenesis. A. True B. False 42-52. Write S if the description applies to the sympathetic division of the ANS, P if it applies to the parasympathetic division, and PS if it applies to both. _____ 42. Also called thoracolumbar outflow _____ 43. Has long preganglionic fibers leading to terminal ganglia and very short postganglionic fibers _____ 44. Celiac and superior mesenteric ganglia are sites of postganglionic neuron cell bodies _____ 45. Sends some preganglionic fibers through cranial nerves _____ 46. Has some preganglionic fibers synapsing in vertebral chain (trunk) _____ 47. Has more widespread effect in the body, affecting more organs _____ 48. Has fibers running in gray rami communicates to supply sweat glands, arrector pili muscles, and blood vessels _____ 49. Has fibers in white rami _____ 50. Contains fibers that supply viscera with motor impulses _____ 51. The greater and lesser splanchnic nerves contain axons of this division _____ 52. The pelvic splanchnic nerves contain axons of this division 53-65. Use arrows to show whether parasympathetic (P) or sympathetic (S) fibers stimulate (↑) or inhibit (↓) each of the following activities. Use a dash (—) to indicate that there is no (or virtually no) parasympathetic innervation. 53. P_____ S_____ Dilation of pupil 54. P_____ S_____ Heart rate and blood flow to coronary blood vessels 55. P_____ S_____ Constriction of blood vessels of skin and abdominal viscera 56. P_____ S_____ Salivation and digestive organ contractions 57. P_____ S_____ Erection or engorgement of genitalia 735 58. P_____ S_____ Dilation of bronchioles for easier breathing 59. P_____ S_____ Contraction of bladder and relaxation of internal urethral sphincter causing urination 60. P_____ S_____ Contraction of arrector pili of hair follicles causing “goose bumps” 61. P_____ S_____ Contraction of spleen which transfers some of its blood to general circulation, causing increase in blood pressure 62. P_____ S_____ Release of epinephrine and NE from adrenal medulla 63. P_____ S_____ Secretion of insulin and digestive enzymes from the pancreas 64. P_____ S_____ Increase in blood glucose level by pancreatic secretion of the hormone glucagon and by formation of glucose in the liver 65. P_____ S_____ Coping with stress, fight-or-flight response 736 66. Complete the sympathetic pathways shown in the diagram below. A preganglionic neuron located at T5 of the cord has its axon drawn as far as the white ramus. Finish this pathway by showing how the axon may branch and synapse to eventually innervate these three organs: the heart, a sweat gland in the skin of the thoracic region, and the stomach. Draw the preganglionic fibers in solid lines and the postganglionic fibers in broken lines. 737 Answers: 1B, 2C, 3C, 4D, 5E, 6B, 7A, 8B, 9E, 10D, 11D, 12E, 13C, 14E, 15C, 16C, 17E, 18B, 19B, 20C, 21C, 22D, 23BC, 24C, 25D, 26E, 27B, 28B, 29C, 30C, 31B, 32A, 33J, 34B, 35B, 36B, 37A, 38B, 39A, 40A, 41A, 42S, 43P, 44S, 45P, 46S, 47S, 48S, 49S, 50PS, 51S, 52P, 53P↓S↑, 54P↓S↑, 55P—S↑, 56P↑S↓, 57P↑S↓, 58P↓S↑, 59P↑S↓, 60P—S↑, 61P—S↑, 62P—S↑, 63P↑S↓, 64P—S↑, 65P↓S↑, 66 see below 738