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General Physiology K. Bedu-Addo, PhD Recommended Books • Review of Medical Physiology- Ganong • Textbook of Medical Physiology- Guyton & Hall • Physiology- Berne et al • Human Physiology- Sherwood • Human Physiology- Vander et al Outline Levels of organization in the Human • Chemical level • Cellular level • Tissue level • Organ level • Organ System level • Organism Body Water • Total body water • Body fluid compartments • Functions of water • Measurement of body fluid compartments Cellular Membranes • Structure • Membrane transport o Diffusion Simple diffusion Ionic diffusion Facilitated diffusion o Active transport Primary active transport Secondary active transport o Vesicular transport Endocytosis Exocytosis o Caveolae o Osmosis o Filtration Homeostasis o Homeostatic control systems o Components of a control system o Strategies for maintenance of homeostasis Nervous Tissues o Nerve Cells Types and classification o Glial cells Types o Resting membrane potential o Action potential Generation Propagation Properties Objectives After going through the general physiology lectures, you should be able to: • describe the levels of organization in the Human • describe how the levels are organized • identify the main body fluid compartments and estimate their volumes • describe the structure and components of plasma membranes • describe the mechanisms involved in the transport of substances across plasma membranes • outline the principles of homeostasis and their application in the human • • • • list the main subdivisions of the nervous system describe the main structure of a neuron name the glial cells and their functions describe resting membrane potential and how it is generated • describe how changes in cell ionic movements produce an action potential • explain propagation of an action potential Physiology: The study of how the body and its parts function Levels of Organization in the Human The arrangement of specialized parts within a living thing is sometimes referred to as levels of organization. The human body has many levels of structural organization. • The simplest level of organization within the body is the chemical level, which is composed of atoms and molecules • Cells are the next level of organization The cell is the smallest structural and functional unit that exhibits the characteristics of living things (organisms) • Tissues: Tissues are the next level of organization in any multicellular organism. Tissues are cells that are similar in structure and function and usually joined together There are four main tissues, these are: Epithelial tissue, which covers exposed surfaces and lines body cavities. Connective tissue, which protects, supports, and interconnects body parts and organs egs bone, blood, cartilage Muscle tissue, which produces movement Nervous tissue, which conducts impulses for internal communication • Organs are the next level of organization organs are different types of tissues that work together to perform a particular function • Organ systems are the next level of organization An organ system is a group of organs that work together to perform a major function There are 11 organ systems in the human body. These are: integumentary skeletal muscular Nervous Endocrine Cardiovascular Lymphatic Respiratory Digestive Urinary Reproductive • The last level of organization is the Organism All body systems function interdependently in a single living human being, the organism Body Water Total amount of water in the body is the total body water (TBW) TBW varies with: • age Declines with age: ≈ 73% of the body weight in infants, ≈ 60% of the body weight in adults • gender 55-60% of the body weight in men 45-50% of the body weight in young women • degree of obesity Correlates inversely with body fat • the percentage of water in the fat-free tissue (‘lean body mass’) is remarkably constant at 73% Daily fluid intake and output In steady state water intake= water loss • Water input ingestion o by drinking (1500 ml/day) o by eating (500 ml/day) o by the metabolism of food (400 ml/day) water intake depends on o climate o habits o level of physical activity • Output insensible water loss o lungs o skin sweating urine feces Body Fluid Compartments TBW is distributed between two major compartments- intracellular and extracellular fluid compartments which are separated by cell membranes Intracellular fluid (ICF) comprises 2/3 of the TBW constitutes about 40% of the body weight found in cells of the body high in potassium, magnesium ions, phosphate and organic anions, proteins and low in sodium and chloride ions Extracellular Fluid (ECF) comprises the remaining 1/3 TBW constitutes about 20% of body weight found outside the cells low in potassium & magnesium ions and high in sodium, chloride and bicarbonate ions The ECF is further subdivided into three subcompartments: o Interstitial Fluid (ISF) surrounds the cells does not circulate comprises about 3/4 of the ECF only compartment that declines with age o Plasma circulates as the extracellular component of blood It makes up about 1/4 of the ECF. o Transcellular fluid It is contained within epithelial lined spaces set of fluids that are outside of the normal compartments It includes CSF, GIT fluids, bladder urine, aqueous humor and joint fluid, peritoneal and pericardial fluids constitute about 0.5 to 2 liters Composition of Body Fluid Compartments Ion Plasma(mmol/L) ICF(mmol/L) Na+ K+ Ca2+ Mg2+ ClHCO3HPO4 2SulfateProteinate- 143 5 1,3 0.9 103 24 0,4 0,4 1,14 9 135 <0,8 25 9 9 74 19 64 Functions of H2O The functions of H2O in human body are vital. It • transports nutrients and oxygen into cells • moisturizes the air in lungs • helps with metabolism • protects our vital organs • helps our organs to absorb nutrients better • regulates body temperature • detoxifies • protect and moisturizes our joints we cannot function without H2O Measurement of body fluid compartment volumes Measurement based on the dilution principle Example: if 25 mg of glucose is added to an unknown volume of distilled water and the final concentration of glucose after mixing is 0.05 mg/ml, then the volume of solvent is? Volume = 25 mg/0.05 mg/ml = 500 ml Corrections Characteristics of Markers • should be water soluble • should be measurable • should remain in the compartment being measured • should not alter water distribution • should not be toxic • must not be secreted by the body • must be unchanged in the body • amount excreted or metabolically degraded must be measurable TBW measured using heavy watero dueterium oxide o tritiated water (tritium oxide) ECF volume measured using: o inulin o mannitol o sucrose etc Plasma volume measured either by using: o radioiodinated human serum albumin (Risa) o Evans blue Interstitial volume cannot be measured directly it is the difference between ECF volume and plasma volume ICF volume cannot be measured directly ICF volume is obtained by subtracting the ECF volume from the TBW Blood Volume o makes about 6-8% body weight of a healthy adult (5 litres) o contains both ECF and ICF o Blood volume is determined by using radioactive isotopes of phosphorus 32P, iron 55,59Fe and chromium 51Cr. o Tagged red cells are injected intravenously and blood volume determined by dilution principle o blood volume can also be calculated from the plasma volume if one knows the hematocrit (the fraction of the total blood volume composed of red blood cells), using the equation: For example, if plasma volume is 3 liters and hematocrit is 0.40, total blood volume would be calculated as Cellular Membranes The cell membrane (also called the plasma membrane, plasmalemma or "phospholipid bilayer") is a semipermeable lipid bilayer found in all cells. It • serves as the attachment point for the intracellular cytoskeleton • is a highly selective barriers that regulate what enters and exits the cell • detects signals • is involved in cell-cell communication • helps in cell identity Structure • Thin, pliable, elastic structure • between 7.5 –10 nm thick • The cell membrane is a fluid mosaic of lipids, proteins, and carbohydrates • the relative amounts of the components depend on the membrane's location and role in the body Lipids • There are three different major classes of lipid molecules: phospholipids cholesterol glycolipids • Different membranes have different ratios of the three lipids o Phospholipids • are the main components of the lipid bilayer • the membrane lipids are relatively small molecules with a hydrophilic (phosphate end) and hydrophobic (fatty acid end) part • The hydrophobic 'tails' of many phospholipids align next to, and opposite each other, forming a bilayer of phospholipid molecules with hydrophilic 'heads' pointing outwards • The entire membrane is held together by noncovalent interaction of hydrophobic tails • the structure is quite fluid and not fixed rigidly in place • The bilayer is impenetrable to water soluble molecules and ions • The right ratio of saturated to unsaturated fatty acids keeps the membrane fluid at any temperature conducive to life • Four groups of phospholipids make up most of the plasma membrane, these are: phosphatidylcholine phosphatidylethanolamine phosphatidylserine sphingomyeline • phosphatidylinositols are present in small quantities o Cholesterol • steroid lipids • interdigitate between and have same orientation as the phospholipid molecules • Reduces membrane fluidity by reducing phospholipid movement • provides mechanical stability to the membranes • decreases membrane permeability to small water-soluble molecules • lowers the temperature required for the membrane to solidify, contributing to fluidity Proteins Membrane proteins are classified into two major categories ─ Integral and Peripheral proteins o Integral proteins attached to lipids in the bilayer by their hydrophobic portions transmembrane proteins- have hydrophobic regions that completely span the hydrophobic interior of the membrane. The hydrophilic ends of the molecule are exposed to the aqueous solutions on either side of the membrane monotopic proteins- are only embedded into one side of the cell membrane o Peripheral proteins are not embedded in the lipid bilayer completely on membrane surface they form ionic and H-bond interactions with hydrophilic lipid and protein groups can be removed with high salt or alkaline solutions • Plasma membrane proteins have several functions channels carrier proteins receptors enzymes cell adhesion molecules (CAM) gap junctions desmosomes tight junctions antigens surface recognition cytoskeleton contact Carbohydrates • About 3% of the plasma membrane weight is carbohydrate • They are usually branched oligosaccharides with fewer than 15 sugar units • Some are covalently bonded to lipids, forming glycolipids • Most are covalently bonded to proteins, forming glycoproteins • the carbohydrate forms a loose coat on the membrane called glycocalyx • Face away from cytoplasm (on outside of cell) • Plasma membrane carbohydrates function in several different ways receptors cell adhesion molecules surface recognition may be involved in immune reaction The plasma membrane is asymmetrical Eg. Intestinal epithelial cell membrane • Apical surface selectively absorbs materials Contains specific transport proteins • Lateral surface interacts with neighboring cells Contains junction proteins to allow cellular communication • Basal surface sticks to extracellular matrix and exchanges with blood Contains proteins for anchoring Membrane Transport Cell membranes are differentially (or semi-) permeable barriers separating the inner cellular environment from the outer cellular (or external) environment. • Permeation of particles across cell membranes is dependant on two properties ─ the relative solubility of the particle in lipid the size of the particle • Transport across the plasma membrane is governed by two basic processes. These are: diffusion active transport Diffusion Diffusion is the spontaneous movement of material from a region of high concentration to a region of low concentration • Diffusion across membranes is either by simple diffusion or facilitated diffusion Simple Diffusion It refers to a process whereby a substance passes through a membrane without the aid of an intermediary such as a integral membrane protein. • lipid/non polar soluble substances cross cell membranes readily than water soluble substances • cell membranes are impermeable to large water soluble substances • the direction of movement of non electrolytes is along a concentration gradient • Ions are relatively lipid insoluble. Ionic diffusion is via protein channels in plasma membranes • ionic diffusion depends on the electrical and concentration/chemical gradients ie electrochemical gradient Facilitated diffusion eg glucose, amino acids • Like simple diffusion net flux is down an electrochemical gradient • requires a membrane carrier that spans the thickness of the membrane • requires no metabolic energy input • exhibits characteristics of carrier-mediated transport more rapid than simple diffusion saturation specificity competition inhibition Active transport • In active transport substances are moved against their electrochemical gradient • requires a carrier protein • requires energy • exhibits characteristics of carrier-mediated transport • Two types ─ Primary and secondary active transports Primary Active Transport • Utilizes metabolic energy in the form of ATP eg Na+-K+ATPase, Ca2+ATPase, H+-K+ATPase Secondary Active Transport • indirect utilization of metabolic energy • This utilizes the energy released during the passive movement of one substance down its electrochemical gradient to transport another substance against a concentration gradient eg co-transport of Na+ and glucose, cotransport of Na+ and amino acids There are several types of membrane transport proteins. o Uniports They move one kind of solute across the lipid bilayer o Cotransport systems • They work by simultaneously sending two or more different solutes across the lipid bilayer • There are two types of cotransport systems – symport- the solutes are sent in the same direction antiport- the solutes are sent in opposite directions. Vesicular Transport • Movement of macromolecules within membranebound vesicles across cell membranes • The are two main types─ endocytosis and exocytosis Endocytosis Uptake of macromolecules • There are three types of endocytosis: phagocytosis, pinocytosis, and receptor-mediated endocytosis • The material to be internalized is surrounded by an area of plasma membrane, which then buds off inside the cell to form a vesicle • Molecule responsible for pinching off is dynamin • It requires metabolic energy Exocytosis The process by which materials packaged in vesicles are secreted from a cell when the vesicle membrane fuses with the plasma membrane • requires energy • requires Ca2+ Osmosis The passive diffusion of water across a semipermeable membrane from a region of low solute concentration to a region of high solute concentration ie the passage of water from a region of high water concentration through a semipermeable membrane to a region of low water concentration. • Presence of solute results in a decrease in the chemical potential of water • osmosis generates a pressure called osmotic/ hydrostatic ('water-stopping') pressure. • Osmotic pressure is defined as the hydrostatic pressure required to stop the flow of water • If the pressure in the compartment into which water is flowing is raised to the equivalent of the osmotic pressure, movement of water will stop • osmotic pressure is dependant on the number of particles in solution • If the total osmotic pressure of two solutions are equal, they are said to be isotonic • If solution A has a greater osmotic pressure than solution B, A is said to be hypertonic to B • If solution A has a less osmotic pressure than solution B, A is said to be hypotonic to B • water diffuses rapidly through cell membranes by utilizing aquaporins- a group of transmembrane proteins in the membrane Filtration The process by which fluid is forced through a membrane/barrier because of differences in pressure on the two sides. The amount of fluid filtered is proportionate to • the pressure difference • surface area of the membrane • permeability of the membrane Homeostasis Maintenance of a constant internal environment • The concept was created by Claude Bernard who proposed the principle of the constancy of the milieu interieur in 1878. • The term was coined in 1932 by Walter Cannon from the Greek words homeo (same, like, resembling) and stasis (to stand, posture). • the ECF is considered to be the internal environment • The essential variables of the internal environment that are maintained within limits acceptable are: Concentration of oxygen and carbon dioxide pH of the internal environment Concentration of nutrients and waste products Concentration of salt and other electrolytes Volume and pressure of extracellular fluid temperature • Homeostasis is continually disturbed by stress • Much disease results from disturbance of homeostasis, a condition known as homeostatic imbalance. • Homeostasis depends on the action and interaction of a number of body systems to maintain a range of conditions within which the body can best operate. These organ systems are the: integumentary system circulatory system lymphatic system and immunity digestive system nervous system endocrine system reproductive system muscular and skeletal systems respiratory system excretory system • the nervous system and to some degree the endocrine system are the main control systems of homeostasis • homeostasis allows humans to live in many habitats Homeostatic Control Systems Homeostatic control systems are body components that generate compensatory regulatory responses to maintain relatively stable conditions of the internal environment • they are subject to nervous and endocrine control • homeostatic control systems have three components. They are: o detectors/sensors o integrating center o effectors • Two basic strategies are used by the body to maintain homeostasis. These are: Feedback Feedforward Feedback Control The course of a reaction is controlled by the activity of some of the products of the reaction ie the output should have some control over the input. • Feedback control can be either negative or positive Negative Feedback This occurs when a change in a controlled variable triggers a response that opposes the change • Homeostasis primarily operates on this principle • Negative feedback helps to maintain equilibrium • Disruption of negative feedback can lead to undesirable results Positive Feedback This occurs when a change in a controlled variable triggers a response that amplifies the change • Brings about disequilibrium • Not involved in homeostasis • At times, makes negative feedback more efficient Feedforward Control This is a response in anticipation of a change in a controlled variable. The disturbance is suppressed before it has had the chance to affect the system's essential variables • improves the speed of the body’s homeostatic responses • minimizes fluctuations in the level of variable being regulated Excitable Tissues These are tissues that are capable of producing electrical signals when excited. Excitability of cells and tissues is a basic function of life. Excitable tissues include: • Nerves • Muscles • Sensory Receptors Nerve Cells The nervous system consists of neurons and glial cells. Glial cells outnumber the neurons by 1 to 10 Neurons Neurons also known as neurones and nerve cells are electrically excitable cells in the nervous system that process and transmit information A typical neuron has all the parts that any cell would have, and a few specialized structures (soma, dendrites and axon) that set it apart. o Soma/cell body the metabolic center of the neuron It contains the nucleus, which in turn contains the genetic material in the form of chromosomes o Dendrites extensions from the soma they often look like branches or spikes taper towards the apex the surfaces of the dendrites receive chemical messages from other neurons o Axon a long slender extension from the soma it emerges from the soma at the 'axon hillock’ it is uniform in diameter it conducts electrical impulses away from the soma The distal terminations of axons called telodendria/synaptic end bulb/terminal buttons are specialized in releasing neurotransmitters Axons may be myelinated or unmyelinated • myelinated neurons have neurilemma or sheath of glial cells wrapped around the axon to form the myelin sheath • unmyelinated neurons have glial cells but are without the dense membrane wrapping which characterizes myelinated neurons Classification of neurons They are often classified according to function, structure and type of transmitter released Functional Classification Based on the direction of travel of nerve impulse relative to CNS. Functionally there three broad categories of neurons. These are: • Sensory/Afferent neurons convey information from tissues and organs to the central nervous system • Motor/Efferent neurons transmit signals from the central nervous system to the effector cells Has two branches: o somatic system o autonomic system, subdivided into: • sympathetic • parasympathetic • Interneurons are the neurons that provide connections between sensory and motor neurons, as well as between themselves The neurons of the central nervous system, including the brain, are all interneurons Structural classification Based on the number of processes off the cell body. Structurally there are three classes of neurons • Unipolar (or pseudounipolar) neurons. These have one short process that immediately divides into two very long processes both of which are axons they are common These cells are found in the spinal ganglia of the spinal nerves (dorsal root ganglia) as well as in several of the sensory nuclei of the cranial nerve nuclei. These cells bring sensory information into the central nervous system • Bipolar cells these cells consist of a single axon and a single dendrite (two processes) they are rare These cells are found in the retina of the eye and olfactory epithelium cells as well as in several of the cranial nerves • Multipolar neurons they are the most common type they have multiple dendritic processes which give them an irregular shape each neuron has only one axon examples: spinal motor neurons, pyramidal neurons, Purkinje cells Neurotransmitter secreted Neurons can also be classified based on their chemistry - the neurotransmitter(s) they release o cholinergic neurons o adrenergic neurons o peptidergic neurons o purinergic neurons o nonadrenergic/noncholinergic (NANC) Glial Cells Glial cells provide support and protection for neurons. The four main functions of glial cells are: surround neurons and hold them in place supply nutrients and oxygen to neurons insulate one neuron from another destroy and remove the carcasses of dead neurons (clean up) • The four types of CNS supporting cells are Astrocytes o they give nutritional support to the CNS o Form the blood-brain barrier (by holding together neurons and blood vessel with a separation into a two-layered structure) Oligodendrocytes o Form the myelin sheath around axons of the CNS o Help to hold nerve fibers together Microglia Phagocyte cells that migrate through the CNS removing foreign matter and degenerated brain tissue Ependymal cells o Epithelial cells that line the ventricles of the brain and spinal cord o form cerebrospinal fluid and aid in its circulation • The supporting cells of the PNS are: Schwann Form myelin sheaths around peripheral axons Satellite cells Support neurons in the PNS Resting Membrane Potential Membrane potential is the electrical potential difference (voltage) across a cell's plasma membrane as a result of separation of charges across the membrane. The potential difference across a resting cell is the resting membrane potential of the cell. • An insignificant fraction of the total number of charged particles present in the body fluids is responsible for the membrane potential • the resting potential has a negative value, which by convention means that there is excess negative charge inside compared to outside • the magnitude varies from -9 mV to -100 mV • a resting cell is said to be polarized Measurement of MP Generation of the resting potential Membrane potentials in cells are determined primarily by three factors: the unequal distribution of K+, Na+, Cl-, and large intracellular anions across the membrane the permeability of the cell membrane to those ions (i.e., ion conductance) through specific ion channels the activity of electrogenic pumps (e.g., Na+/K+-ATPase and Ca2+ transport pumps) that maintain the ion concentrations across the membrane. Two transport proteins are primarily responsible for the resting membrane potential a K+ leak channel (80%) The membrane of a resting cell is about 5075 times permeable to K+ than it is to Na+ the Na+/K+ ATPase (ion pump) (20%) o direct (electrogenic effect) o indirect (creation of the concentration gradients) MP=0 K+ ECF + + + + + + + - K+ K+ AICF ECF + + + + + + + K+ A- - ICF MP=-90 mV K+ + + + + + + + - K+ A- K+ + + + + + + + - K+ A- • The movements of ions across membranes are influenced by two energetic factors. These are: the concentration gradient the electrical potential difference across the membrane • For a specific ion, the electrical potential difference that exactly counterbalances diffusion due to the concentration difference is called the equilibrium potential for that specific ion. • The equilibrium potential can be calculated from the Nernst equation where Ex is the equilibrium potential for ion X [Xo] is the concentration of X outside the cell [Xi] is the concentration of X inside the cell zx is the valence of ion X R is the gas constant T is the absolute temperature F is Faraday's constant The equilibrium potential for K+ is -90 mV Na+ is +60 mV Cl- is -70 mV The measured resting membrane potential of a neuron is -70 mV The cell's resting membrane potential combines all relevant ion currents with K+ ions figuring most prominently due to their high resting conductance In addition a small number of Na+ ions leak into the cell. The resulting resting membrane potential is thus slightly lower compared to the EK+ at around -70mV The concentration gradient across the membrane is maintained by the Na+/K+ ATPase (ion pump) In the presence of several different ions, resting membrane potential can be calculated using the Goldman-Hodgkin-Katz equation: where V = The membrane potential Pion = the permeability for that ion [ion]out = the extracellular concentration of that ion [ion]in = the intracellular concentration of that ion R = The ideal gas constant T = The temperature in kelvins F = Faraday's constant • Increasing the external K+ concentration decreases the resting membrane potential • Decreasing the external Na+ concentration has little effect on the resting membrane potential Action Potential • Two types of responses can be elicited if a nerve cell is stimulated. These are: o Graded/local/electrotonic/generator potential o Action potential • The type of response depends on the intensity of stimulation. Graded Potentials A non propagating, localized potential difference across the membrane of a neuron • it declines with time and distance from the stimulus point • elicited by a stimulus of subthreshold strength • arise mainly in dendrites and cell bodies • there is no reversal of polarity • amplitude depends on strength of stimulus; varies from less than 1 mV to more than 50mV • typically longer duration, ranging from msec to several minutes • may be hyperpolarizing (inhibitory to generation of action potential) or depolarizing (excitatory to generation of action potential) • has no refractory period • exhibit temporal and spatial summation Action Potential A self-propagating electrical potential difference produced across the plasma membrane of nerve or muscle cells when they are stimulated • an action potential is initiated by a stimulus above a certain intensity or threshold • there is a transient reversal of polarity • arise at trigger zones and propagate along axon • propagated, thus permit communication over long distances • all or none, typically 100 mV • typically of shorter duration, ranging from 0.5 – 2 msec • always consist of depolarizing phase followed by repolarizing phase and then return to resting membrane potential • has a refractory period • not subject to summation Phases of the AP • Latent period • Depolarization • Repolarization • After-hyperpolarization Latent Period Isoelectric interval. Time taken by stimulus to travel from point of stimulation to the recording electrode Depolarization A depolarization of adequate rate and threshold o causes the voltage-gated Na+ channels to open making the membrane 4-5000-fold permeable to Na+ and driving the interior potential from -70 mV up to – 55 mV, o having reached the action threshold, more voltage-gated Na+ channels open by a positive feedback effect o the Na+ influx drives the interior of the cell membrane up to about +40 mV o voltage-gated K+ channels also open. Since the K+ channels are much slower to open, the depolarization has time to be completed. Repolarization o the Na+ channels show rapid inactivation for some time, resulting in a significant decrease in Na+ conductance before closing o repulsion of Na+ by the positive interior limits influx of Na+ o prolonged opening of the voltage-gated K+ channels increases K+ conductance and returns the potential back to the resting level After-hyperpolarization With both the voltage-gated and non-gated K+ channels open, the membrane potential becomes more negative than the resting potential The RP is regained by closure of the voltage-gated K+ channels efflux of K+ through non-gating K+ channels restoration of resting ion concentrations by the Na+-K+ pump Decreasing the external Na+ concentrations decreases the size of the AP Propagation of APs • once an AP is generated at one site, it is conducted along the axon • conduction is by local current flow • The new action potential produces local currents • positive charges inside the cell spread from the active site toward negative charges at the adjacent inactive site • these attract negative ions away from the adjacent membrane • this current flow causes the adjacent region to depolarize to threshold generating another AP • the process repeats itself down the length of the axon, with an action potential regenerated at each segment of membrane Factors affecting speed of propagation of AP The speed of conduction can be influenced by: the diameter of a fiber the presence or absence of myelin temperature Diameter Increasing the radius of the axon increases conduction velocity. • This is explained by the relationship which states that the internal resistance R is inversely proportional to the cross-sectional area: o thus the larger the fiber the lower the internal resistance o and thus the greater the conduction velocity o the conduction velocity in unmyelinated axons is proportional to the square root of the axon diameter o current flow is facilitated in large-diameter axons because of the high intracellular ion mobility Presence or absence of myelin Myelination has two effects o it decreases the leakiness of the membrane to ions, as a result it’s very difficult for ions to pass out of the axons except where there is no myelin- ie at the nodes of Ranvier o it greatly reduces the ability of the membrane to store charge ie it reduces membrane capacitance. As a result there is little accumulated charge near the membrane to slow down current flow within the axon o Both of these features greatly speed up the rate of propagation of the AP in a myelinated axon Temperature o increasing the temperature increases ion flow and the probability of the membrane being polarized o temperature has large effects on the rate of increase of Na+ channel conductance and action potential waveform o channels open and close more slowly at lower temperature, and subsequently conduction velocity is reduced o conduction slows down in cooled nerves Types of conduction There are two types. These are • Regular/Continuous conduction • Saltatory conduction Regular conduction It is a sequential spread of action potential that occurs in unmyelinated axons • action potentials are propagated as waves Saltatory conduction A means by which action potentials are transmitted along myelinated nerve fibers • depolarization occurs only at the nodes of Ranvier where membrane resistance is low • depolarization at one node of Ranvier is sufficient to elevate the voltage at a neighboring node to the threshold for action potential initiation • action potentials do not propagate as waves, but recur at successive nodes and in effect "hop“ along the axon • saves energy by decreasing the use of sodium- potassium pumps in the axonal membrane • faster than regular conduction Refractory Period The period during an action potential when the ability of the membrane to respond to a second stimulus is markedly altered • it limits the number of APs that can be produced by an excitable membrane in a given period • it is a key in determining the direction of AP propagation • It is made up of two phases. These are: absolute refractory period relative refractory period Absolute Refractory Period It is the period during an action potential, when a second stimulus will not produce a second action potential no matter the strength of the stimulus • it corresponds to the period when the voltage-gated Na+ channels are open or in the inactivation state • coincides with the entire duration of the action potential Relative Refractory Period It is the period during an action potential when another action potential can be produced, but only if the stimulus strength is greater than the threshold stimulus, then gradually by stimuli of progressively lesser magnitude • during this period some but not all of the voltage-gated Na+ channels have returned to the resting state • it corresponds to the period when the potassium channels are open (several milliseconds) • it coincides roughly with the period of afterhypolarization when the membrane potential becomes transiently more negative than the normal resting potential Accommodation The property of a nerve by which it adjusts to a slowly increasing level of stimulus, so that its threshold of excitation is greater than it would be were the stimulus level to have risen more rapidly • both Na+ and K+ channels are involved • critical number of open Na+ channels required to trigger an AP is not attained during slow depolarization • increased K+ conduction during depolarization tends to repolarize the membrane Organization of the Nervous System The nervous system orchestrates body functions to maintain homeostasis • it is made up of neurons and glial cells Functions • controls and coordinates the body functions • it processes the incoming sensory information and generate an appropriate motor response to adjust activity of muscles and glands • keeps the previous stimuli as the experiences or memory which guide the animal in future • coordinates the visceral functions to maintain a homeostasis in the body Divisions The nervous system is divided into: • Central nervous system (CNS) • Peripheral nervous system (PNS) CNS • consists of the brain and the spinal cord • is the control center of nervous system interpreting, integrating, and issuing commands to the other branches of the nervous system • encased in bone and protected by CSF and the meninges PNS includes all parts of the nervous system not covered by bone • carries out sensory and motor functions • contains 12 pairs of cranial and 31 pairs of spinal nerves, and sensory receptors throughout the body • has two subdivisions: o Sensory (Afferent) o Motor (Efferent) Sensory Division contains sensory receptors and nerves which carry information to the CNS Motor Division sends information from the CNS to the body´s effectors ( muscles, organs, and glands ) o Has two subsystems Somatic Nervous system Autonomic nervous System Somatic nervous system consists of nerves that carry information to skeletal muscles which control voluntary movement Autonomic Nervous System consists of nerves that carry information to visceral organs and glands o their activities are outside conscious control o has two branches: sympathetic: fight and flight division parasympathetic: rest and digest division The Human Brain • It is the site of major coordination in the nervous system • it contains around 100 billion neurons linked to up to 10,000 synaptic connections • weighs about 1.36 kg in adults • there are four main areas of the brain: o cerebrum o cerebellum o brain stem o diencephalon Cerebrum • above the diencephalon • the largest division of the brain • consists of two sides, the right and left cerebral hemispheres, which are interconnected by the corpus callosum • the hemispheres are covered by a thin layer of gray matter known as the cerebral cortex • each hemisphere of the cerebral cortex is divided into four lobes called: o occipital o temporal o parietal o frontal Frontal lobe • most anterior, right under the forehead • controls: motor activity and integration of muscle activity speech (left hemisphere) thought processes Parietal Lobe • near the back and top of the head • coordinates afferent information dealing with: pain temperature form/shape texture pressure position • Some memory functions are also found here Temporal lobe • side of head above ears • handles: dreams memory emotions • center for auditory function • involved in processing language and the meaning of words • olfactory function Occipital Lobe • most posterior, at the back of the head • receives and processes visual information Diencephalon • located between the cerebrum and the midbrain • contains the: o thalamus o hypothalamus Thalamus • large, bilateral egg-shaped mass of gray matter • serves as the main synaptic relay center • receives/relays sensory information to/from the cerebral cortex Hypothalamus: • a collection of ganglia located below the thalamus • intimately associated with the pituitary gland • controls: water homeostasis temperature homeostasis autonomic activities • links the nervous system to the endocrine system via the pituitary gland • acts as an endocrine gland • regulates appetite Cerebellum • the second largest brain structure • sits below the cerebrum • has an outer cortex of gray matter • has two hemispheres • receives/relays information via the brain stem • controls: balance/equilibrium of the trunk muscle tension spinal nerve reflexes posture and balance of the limbs fine motor control eye movement Brainstem • controls the most basic life functions • it is the base of the brain • it adjoins the spinal chord • contains the: o medulla oblongata o pons o mid brain Medulla oblongata Controls: • heart rate/action • vasoconstriction/blood vessel diameter • breathing • peristalsis • reflexes such as: swallowing coughing sneezing vomiting hiccupping Pons Controls: • breathing • reflexes such as: pupillary reflexes eye movements Midbrain Controls • reflexes such as: pupillary reflexes eye movements THE LIMBIC SYSTEM. The part of the brain that regulates emotion and memory • a complex set of structures that lies on both sides of the thalamus, just under the cerebrum • it directly connects lower and higher brain functions • horseshoe-shaped • it includes the: o Thalamus o Hypothalamus o Cingulate gyrus o Amygdala o Hippocampus o Basal Ganglia o the olfactory bulb and other areas of the brain are considered part of the limbic system • the limbic system is concerned with emotional states (such as rage, fear and memory). The hippocampus, in particular, plays a vital role in learning and long-term memory The Spinal Chord • a large, nearly circular mass of nerve tissue which runs along the dorsal side of the body • links the brain to the rest of the body • encased in the vertebral column • the gray matter of the spinal cord consists mostly of cell bodies and dendrites • the surrounding white matter is made up of bundles of interneuronal axons (tracts) • has two functions: o provides the two-way conduction routes to/from (afferent/efferent) the brain o serves as the reflex center for all spinal reflexes