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Mammalian Physiological (Bio 440) Overview of the Heart -Fundamentals of the cardiovascular system -Compare skeletal, cardiac and smooth muscle with respect to histology and neurogenic vs. myogenic activity. -Fundamentals of the circulatory system Neurogenic – extrinsic initiation of muscle activity Myogenic – intrinsic initiation of muscle activity UNLV UNIVERSITY OF NEVADA LAS VEGAS Mammalian Physiological (Fundamentals) 1) The heart sits at the center of the universe why? Because I am a cardiovascular physiologist! 2) The mammalian heart has four chambers 2 – ventricles and 2 – atria 3) The right and left hearts are separate and distinct with unique circulations and pressures 4) Their flows, however, must be equal! Why? 5) Anatomical and histological design of the heart and circulatory system. 6) Cardiac cycle 7) Vascular dynamics and regulation Mammalian Physiological (Fundamentals) 1) The heart sits at the center of the universe why? Because I am a cardiovascular physiologist! 2) The mammalian heart has four chambers 2 – ventricles and 2 – atria 3) The right and left hearts are separate and distinct with unique circulations and pressures 4) Their flows, however, must be equal! Why? 5) Anatomical and histological design of the heart and circulatory system. 6) Cardiac cycle 7) Vascular dynamics and regulation Mammalian Physiological (Fundamentals) Mammalian Physiological (Fundamentals) 1) The heart sits at the center of the universe why? Because I am a cardiovascular physiologist! 2) The mammalian heart has four chambers 2 – ventricles and 2 – atria 3) The right and left hearts are separate and distinct with unique circulations and pressures 4) Their flows, however, must be equal! Why? 5) Anatomical and histological design of the heart and circulatory system. 6) Cardiac cycle 7) Vascular dynamics and regulation Systemic circuit Pulmonary circuit Mammalian Physiological (Fundamentals) 1) The heart sits at the center of the universe why? Because I am a cardiovascular physiologist! 2) The mammalian heart has four chambers 2 – ventricles and 2 – atria 3) The right and left hearts are separate and distinct with unique circulations and pressures 4) Their flows, however, must be equal! Why? 5) Anatomical and histological design of the heart and circulatory system. 6) Cardiac cycle 7) Vascular dynamics and regulation Mammalian Physiological (Fundamentals) 1) The heart sits at the center of the universe why? Because I am a cardiovascular physiologist! 2) The mammalian heart has four chambers 2 – ventricles and 2 – atria 3) The right and left hearts are separate and distinct with unique circulations and pressures 4) Their flows, however, must be equal! Why? 5) Anatomical and histological design of the heart and circulatory system. 6) Cardiac cycle 7) Vascular dynamics and regulation Mammalian Physiological (Fundamentals) 1) The heart sits at the center of the universe why? Because I am a cardiovascular physiologist! 2) The mammalian heart has four chambers 2 – ventricles and 2 – atria 3) The right and left hearts are separate and distinct with unique circulations and pressures 4) Their flows, however, must be equal! Why? 5) Anatomical and histological design of the heart and circulatory system. 6) Cardiac cycle 7) Vascular dynamics and regulation Mammalian Physiological (Fundamentals) 1) The heart sits at the center of the universe why? Because I am a cardiovascular physiologist! 2) The mammalian heart has four chambers 2 – ventricles and 2 – atria 3) The right and left hearts are separate and distinct with unique circulations and pressures 4) Their flows, however, must be equal! Why? 5) Anatomical and histological design of the heart and circulatory system. 6) Cardiac cycle 7) Vascular dynamics and regulation Mammalian Physiological (Fundamentals) 1) The heart sits at the center of the universe why? Because I am a cardiovascular physiologist! 2) The mammalian heart has four chambers 2 – ventricles and 2 – atria 3) The right and left hearts are separate and distinct with unique circulations and pressures 4) Their flows, however, must be equal! Why? 5) Anatomical and histological design of the heart and circulatory system. 6) Cardiac cycle 7) Vascular dynamics and regulation Mammalian Physiological (Fundamentals) 1) The heart sits at the center of the universe why? Because I am a cardiovascular physiologist! 2) The mammalian heart has four chambers 2 – ventricles and 2 – atria 3) The right and left hearts are separate and distinct with unique circulations and pressures 4) Their flows, however, must be equal! Why? 5) Anatomical and histological design of the heart and circulatory system. 6) Cardiac cycle 7) Vascular dynamics and regulation Mammalian Physiological (Fundamentals) 1) The heart sits at the center of the universe why? Because I am a cardiovascular physiologist! 2) The mammalian heart has four chambers 2 – ventricles and 2 – atria 3) The right and left hearts are separate and distinct with unique circulations and pressures 4) Their flows, however, must be equal! Why? 5) Anatomical and histological design of the heart and circulatory system. 6) Cardiac cycle 7) Vascular dynamics and regulation Mammalian Physiological (Fundamentals) 1) The heart sits at the center of the universe why? Because I am a cardiovascular physiologist! 2) The mammalian heart has four chambers 2 – ventricles and 2 – atria 3) The right and left hearts are separate and distinct with unique circulations and pressures 4) Their flows, however, must be equal! Why? 5) Anatomical and histological design of the heart and circulatory system. 6) Cardiac cycle 7) Vascular dynamics and regulation The Heart Muscle: The heart as a pump (Moving blood) Neurogenic Muscle: Contracts in response to direct nervous input or stimulation via neurohormones. Skeletal Muscle Smooth Muscle UNLV UNIVERSITY OF NEVADA LAS VEGAS Neurogenic Muscle UNLV UNIVERSITY OF NEVADA LAS VEGAS E-C coupling – excitation-contraction coupling The Heart as a Muscle 2 - Action Potentials in Cardiac Muscle 1 - Myocardial Syncytium UNLV UNIVERSITY OF NEVADA LAS VEGAS 3 - Excitation-Contraction Coupling How does the Heart know to Contract? Automaticity of pacemaker cells, Conducting system of the heart and Myocardium Myogenic Muscle: Contracts spontaneously Standard Skeletal Muscle (Neurogenic) UNLV UNIVERSITY OF NEVADA LAS VEGAS 1 - Myocardial Syncytium Myocardial Syncytium (Functional syncytium) Cardiac Tissues -Heart is composed of several types of tissue: Epithelial – covers and lines the heart (epicardium, endocardium) Connective Tissue - covers the heart as pericardium and acts as cardiac skeleton Muscle UNLV UNIVERSITY OF NEVADA LAS VEGAS -contractile tissue, myocardium (myocytes), conducting system of the heart Myocardial Syncytium (Functional syncytium) Myocardium (contractile tissue) -Cardiac muscle cells differ from skeletal muscle cells: shorter (smaller cells) single or double nuclei intercalated discs gap junctions -Cardiac muscle cells are similar to skeletal muscle cells: sarcolemma contractile mechanism similar T-tubules SR UNLV UNIVERSITY OF NEVADA LAS VEGAS Myocardial Syncytium (Functional syncytium) Functioanl syncytium: -2 functional syncytia: UNLV UNIVERSITY OF NEVADA LAS VEGAS -atrial & ventricular -separated by fibrous CT -connected by A-V bundle Myocardial Syncytium (Functional syncytium) Distinct electrical signatures -Slow response potentials -Fast response potentials UNLV UNIVERSITY OF NEVADA LAS VEGAS Cardiac Action Potentials Cardiac Action Potentials 1 - Slow response -sinoatrial node (SA) -atrioventricular node (AV) 2 - Fast response -atrial myocytes -ventricular myocytes -Purkinje fibers UNLV UNIVERSITY OF NEVADA LAS VEGAS Note: (1) fast response resting potential more Negative. (2) slope of phase 0. (2) amplitude. (3) overshoot all greater than slow response. Cardiac Action Potentials Cardiac Action Potentials 1 - Slow response -sinoatrial node (SA) -atrioventricular node (AV) 2 - Fast response -atrial myocytes -ventricular myocytes -Purkinje fibers UNLV UNIVERSITY OF NEVADA LAS VEGAS Note: (1) fast response resting potential more Negative. (2) slope of phase 0. (2) amplitude. (3) overshoot all greater than slow response. Cardiac Action Potentials (The basics) Millivolts 1 2 2 0 0 3 0 4 4 -80 (a) (b) Fast response (a) Slow response Time (msec) UNLV UNIVERSITY OF NEVADA LAS VEGAS (b) (a) Effective refractory period (b) Relative refractory period Fast Response Action Potentials Phase 0: 1 -resting membrane potential to a critical value (threshold) -fast Na+ channels opening (tetrodotoxin blocks) -regulated by 2 types of gates -activation gates (m gate) opens when less negative (0.1 msec) -inactivation gates (h gates) close when more negative (few msec) -h gates remain closed until the cell has partially repolarized (phase 3) = Effective refractory period 2 0 4 -Effective refractory period cell will not respond to further excitation UNLV UNIVERSITY OF NEVADA LAS VEGAS -prevents sustained, tetanic contraction which would retard ventricular relaxation and interfere with normal pumping -midway through phase 3 – m and h gates have resumed their initial state (recovered from inactivation) Fast Response Action Potentials Phase 1: 1 -early, brief period of limited repolarization -transient outward current (carried by K+) -phase 1 seen best in ventricular Purkinje fibers 2 0 4 UNLV UNIVERSITY OF NEVADA LAS VEGAS Fast Response Action Potentials Phase 2: 1 2 0 4 -plateau of the action potential -the result of Ca2+ entry into myocardial cells through “calcium channels”, voltage regulated -activate and inactivate more slowly than fast Na+ channels -influx of Ca2+ counterbalanced by efflux of K+ -K+ close - Inward rectifying current, delayed rectifier -L-type Ca2+ channels -inactivates slowly – current “L”ong lasting *the influx of Ca2+ during the plateau phase is involved in excitation-contraction coupling UNLV UNIVERSITY OF NEVADA LAS VEGAS Fast Response Action Potentials Phase 2: 1 -Calcium conductance gCa influenced by many drugs etc. -norepinephrine – adrenergic neurotransmitter -isoproterenol – Β-adrenergic receptor agonist -catecholamines 2 0 4 -Β-adrenergic receptors -stimulates membrane bound adenylyl cyclase -increases intracellular cAMP -enhances activation of L-type Ca2+ channels -acetylcholine UNLV UNIVERSITY OF NEVADA LAS VEGAS -muscarinic receptors -inhibit adenylyl cyclase -antagonize activation of Ca2+ channels Fast Response Action Potentials Phase 2: 1 2 0 4 -Calcium channel antagonists substances that block Ca2+ channels -verapamil -decrease calcium conductance thus impeding the influx of Ca2+ into the myocardial cells -decrease duration of the action potential plateau -diminish strength of cardiac contraction -after-load reducing drugs – reduce vascular smooth muscle contraction (vasodilation) -reduce resistance UNLV UNIVERSITY OF NEVADA LAS VEGAS Fast Response Action Potentials Phase 3: 1 2 0 4 Phase 4: -repolarization -efflux of K+ exceeds the influx of Ca2+ -initiate repolarization and determine the duration of the plateau phase (outward K+ currents) -transient outward current -delayed rectifier current* responsible for variability in different cell types -greater the K+ current during plateau phase 2 the the earlier repolarization begins (atrial myocytes) -excess Na+ that enters during phase 0 is eliminated by Na+/K+-ATPase (3Na+ out for 2K+ in) -excess Ca2+ by Na+/Ca2+ exchanger (3Na+ in for 1Ca2+ out) and Ca2+ ATP pump UNLV UNIVERSITY OF NEVADA LAS VEGAS Slow Response Action Potentials Phase 1: Phase 2: Phase 3: Phase 3-4: -upstroke much less steep -absent -less prolonged and not as flat -transition from plateau to repolarization less distinct SA and AV nodes - depolarization is primarily due to influx of Ca2+ through Ca2+ channels - repolarization is due to inactivation of Ca2+ channels and increased K+ conductance 2 0 UNLV UNIVERSITY OF NEVADA LAS VEGAS 3 4 Excitation of the heart Automaticity -ability to initiate its own beat Rhythmicity -regularity of pacemaking activity Sinoatrial node – greatest frequency Thus it is the primary pacemaker (atrial pacemaker complex) -8X2 mm -small round cells* and slender elongated cells Cells of the AV junction can also act as a pacemaker under aberrant conditions (0) UNLV UNIVERSITY OF NEVADA LAS VEGAS (4) (3) Excitation of the heart Automaticity -ability to initiate its own beat Rhythmicity -regularity of pacemaking activity Sinoatrial node – greatest frequency Thus it is the primary pacemaker (atrial pacemaker complex) -8X2 mm -small round cells* and slender elongated cells Cells of the AV junction can also act as a pacemaker under aberrant conditions (0) UNLV UNIVERSITY OF NEVADA LAS VEGAS (4) (3) Sinoatrial Node Phase 4: -much less negative in SA nodal automatic cells than in atrial or ventricular myocytes due to K+ channels are few in number in nodal cells -phase 4 the potential does not remain constant -pacemaker fibers show a slow diastolic depolarization throughout phase 4 -depolarization proceeds at a steady rate until threshold is attained triggering an action potential -frequency dependent on: (1) rate of depolarization during phase 4 (2) the maximal negativity during phase 4 (3) the threshold potential UNLV UNIVERSITY OF NEVADA LAS VEGAS Sinoatrial Node Ionic basis of automaticity: -Slow diastolic depolarization 1 - inward current if -”funny” current carried by Na+ -activated by greater –50 mV potential 2 – Ca2+ current iCa -activated toward end of phase 4 –55mV -calcium channel activation - influx of Ca2+ -accelerates rate of depolarization 3 – outward current iK -opposed by this current -delayed rectifier K+ -efflux of K+ UNLV UNIVERSITY OF NEVADA LAS VEGAS Autonomic neurotransmitters Automaticity Sympathetic and Parasympathetic Nervous systems: Norepinephrine – raise heart rate by increasing the slope of the slow diastolic depolarization (all three currents) Vagal activity – decreases heart rate - acetylcholine hyperpolarizes the pacemaker cells reducing the slope of the slow diastolic depolarization (increase in gK – acetylcholineregulated K+ channels) (depresses if and iCa currents) UNLV UNIVERSITY OF NEVADA LAS VEGAS Autonomic neurotransmitters Automaticity UNLV UNIVERSITY OF NEVADA LAS VEGAS Electrocardiography (The basics) UNLV UNIVERSITY OF NEVADA LAS VEGAS