CVS Impulse generation 8-Dec-18 CVS Impulse generation

CVS Impulse generation The heart is composed of three types of muscles Atria & ventricles Form the working myocardium They do the mechanical work of pumping 8-Dec-18 CVS Impulse generation

CVS Impulse generation The specialized tissues Excitatory & conducting tissues Sino atrial node Atrio-ventricular node Bundle of his Purkinje fibers 8-Dec-18 CVS Impulse generation

CVS Impulse generation Myocardium Myocardial fibers Excitable tissue Have a resting membrane potential Between –60 to –90 mv Mechanism of genesis of RMP Similar to that in skeletal muscles Cardiac muscle respond To supra threshold stimuli by Generating an action potential Capable of propagating it 8-Dec-18 CVS Impulse generation

CVS Impulse generation Myocardium Excitation arising in atrium or ventricles Spread over the unexcited tissue Works as a syncytium 8-Dec-18 CVS Impulse generation

Cardiac Action Potential General properties of cardiac AP Similar to that of nerve & skeletal muscle Special permeability differences Lead to difference in shape of cardiac AP +20 mv 1 2 0 mv 3 4 - 85 mv 0 = depolarization = initial repolarization Plateau phase repolarization 8-Dec-18 CVS Impulse generation

Cardiac Action Potential In the cardiac cells after the initial spike Membrane remains deoplarized for About 0.2 sec in atria About 0.3 sec in ventricles Exhibiting a plateau +20 mv 1 2 0 mv 3 4 - 85 mv 0 = depolarization = initial repolarization Plateau phase repolarization 8-Dec-18 CVS Impulse generation

Cardiac Action Potential Depolarization Due to  in Na+ conductance Opening of fast sodium channels Initial repolarization Due to closure of sodium channels +20 mv 1 2 0 mv 3 4 - 85 mv 0 = depolarization = initial repolarization Plateau phase repolarization 8-Dec-18 CVS Impulse generation

Cardiac Action Potential The plateau phase Due to slow prolonged opening of Voltage gated Ca++ channels Become activated at potential of –30 to –40 mv Also known as Slow calcium channels Calcium – sodium channels +20 mv 1 2 0 mv 3 4 - 85 mv 0 = depolarization = initial repolarization Plateau phase repolarization 8-Dec-18 CVS Impulse generation

Cardiac Action Potential Large amount of Ca++ & Na+ Flow through these channels Prolong the period of plateau phase +20 mv 1 2 0 mv 3 4 - 85 mv 0 = depolarization = initial repolarization Plateau phase repolarization 8-Dec-18 CVS Impulse generation

Cardiac Action Potential At the end of plateau phase Slow calcium-sodium channels close Influx of Ca++ & Na+ ceases +20 mv 1 2 0 mv 3 4 - 85 mv 0 = depolarization = initial repolarization Plateau phase repolarization 8-Dec-18 CVS Impulse generation

Cardiac Action Potential Permeability of cardiac muscle to K+ increases Efflux of K+ Return the membrane potential to its resting value +20 mv 1 2 0 mv 3 4 - 85 mv 0 = depolarization = initial repolarization Plateau phase repolarization 8-Dec-18 CVS Impulse generation

CVS Impulse generation Refractory Period During the action potential Cardiac muscle is refractory to re-stimulation Cardiac impulse cannot re-excite an already excited area +20 mv 1 2 0 mv 3 4 - 85 mv Absolute refractory period 0.25 – 0.3 sec Relative refractory period 0.05 sec 8-Dec-18 CVS Impulse generation

CVS Impulse generation Refractory Period Normal refractory period 0.25 to 0.3 seconds Approx equal to duration of action potential +20 mv 1 2 0 mv 3 4 - 85 mv Absolute refractory period 0.25 – 0.3 sec Relative refractory period 0.05 sec 8-Dec-18 CVS Impulse generation

CVS Impulse generation Refractory Period Relative refractory period 0.05 seconds During this period Muscle is more difficult to excite But can be excited +20 mv 1 2 0 mv 3 4 - 85 mv Absolute refractory period 0.25 – 0.3 sec Relative refractory period 0.05 sec 8-Dec-18 CVS Impulse generation

CVS Impulse generation Refractory Period Refractory period Is due to inactivation of sodium channels During prolonged depolarization +20 mv 1 2 0 mv 3 4 - 85 mv Absolute refractory period 0.25 – 0.3 sec Relative refractory period 0.05 sec 8-Dec-18 CVS Impulse generation

CVS Impulse generation Refractory Period Not until the membrane Has repolarized to –50 to –60 mv Does sodium channels recover +20 mv 1 2 0 mv 3 4 - 85 mv Absolute refractory period 0.25 – 0.3 sec Relative refractory period 0.05 sec 8-Dec-18 CVS Impulse generation

CVS Impulse generation Refractory Period The cells in SAN Have trans- membrane potential of -55 to –60 mv between discharges SAN cells membrane Naturally leaky to Na+ +20 mv 1 2 0 mv 3 4 - 85 mv Absolute refractory period 0.25 – 0.3 sec Relative refractory period 0.05 sec 8-Dec-18 CVS Impulse generation

CVS Impulse generation Pacemaker Potential Na+ tend to leak into the cell Responsible for the initial phase of pace maker potential Transient (T) Ca++ channels open Entry of Ca++ Completes the pre-potential phase +20 mv 0 mv -50 mv -60 mv Pacemaker potential Ca++ Na+ Ca++ Na+ 8-Dec-18 CVS Impulse generation

CVS Impulse generation Pacemaker Potential The long lasting (L) Ca++ channels then open More Ca++ influx Which produces the impulse +20 mv 0 mv Ca++ -50 mv -60 mv Pacemaker potential Ca++ Na+ Ca++ Na+ 8-Dec-18 CVS Impulse generation

CVS Impulse generation Pacemaker Potential At the peak of each impulse K+ ion channels open Efflux of K+ ions Brings about repolarization K+ +20 mv K+ 0 mv Ca++ -50 mv -60 mv Pacemaker potential Ca++ Na+ Ca++ Na+ 8-Dec-18 CVS Impulse generation

CVS Impulse generation Pacemaker Potential The potassium channels then close Na+ ions leak into the cell Causing the initial phase of pre-potential K+ +20 mv K+ 0 mv Ca++ -50 mv -60 mv Pacemaker potential Ca++ Na+ Ca++ Na+ 8-Dec-18 CVS Impulse generation

CVS Impulse generation Pacemaker Potential Calcium ions channels then Open Calcium influx Completing another deplorization K+ +20 mv K+ 0 mv Ca++ -50 mv -60 mv Pacemaker potential Ca++ Na+ Ca++ Na+ 8-Dec-18 CVS Impulse generation

CVS Impulse generation Spread of Excitation Depolarization initiated in SAN Spread radially through atria Then converge to AVN Atria depolarization Complete in 0.1 second 8-Dec-18 CVS Impulse generation

CVS Impulse generation Spread of Excitation Conduction in AVN is slow Cause 0.1 sec delay AVNodal delay Then the excitation Spread to bundle of His Then to purkinje fibers To the ventricular myocardium 8-Dec-18 CVS Impulse generation

CVS Impulse generation Spread of Excitation The conducting system is such that Cardiac impulse will not travel from atria to ventricle too rapidly Gives time for Atrial emptying before Ventricle contraction begins 8-Dec-18 CVS Impulse generation

Control of Excitation in Heart The pacemaker cells SANode, AVNode, Purkinje cell All exhibit rythmicity Why does the SAN Become the dominant pacemaker Why not The AVNode or Purkinje fibers dominate 8-Dec-18 CVS Impulse generation

CVS Impulse generation Control of Excitation The normal rate of discharge from these cells SAN = 70 to 80 per minute AVN = 40 to 60 per minute Purkinje fibers = 15 to 40 per minute 8-Dec-18 CVS Impulse generation

CVS Impulse generation Control of Excitation In all these cells To change from “resting” to threshold potential Require a change of 20 to 25 mv Thus threshold is reached much faster In SAN than in Purkinje fibers 8-Dec-18 CVS Impulse generation

Factors Affecting the Rate of Pacemaker Rate established by pacemaker cells depend on Time required for membrane pot To change from resting to threshold For generation of AP +20 mv c Threshold pot - 40 mv b d f a - 60 mv e Normal time 8-Dec-18 CVS Impulse generation

Factors Affecting the Rate of Pacemaker Change in heart rate will be mediated by Magnitude of initial “RMP” Rate of depolarization Threshold value +20 mv c Threshold pot - 40 mv b d f a - 60 mv e Normal time 8-Dec-18 CVS Impulse generation

Factors Affecting the Rate of Pacemaker If the “RMP” becomes more negative Shift from (a to e) It takes longer to reach threshold From (e to f) as compared from (a to b) Thus the heart rate Decreases +20 mv c Threshold pot - 40 mv b d f a - 60 mv e Normal time 8-Dec-18 CVS Impulse generation

Factors Affecting the Rate of Pacemaker An increase in the rate of depolarization It takes shorter to reach threshold From (a to c) Compared from (a to b) The heart rate will increase +20 mv c Threshold pot - 40 mv b d f a - 60 mv e Normal time 8-Dec-18 CVS Impulse generation

Factors Affecting the Rate of Pacemaker A shift of threshold potential To a more negative value Will cause an increase in heart rate +20 mv c Threshold pot - 40 mv b d f a - 60 mv e Normal time 8-Dec-18 CVS Impulse generation

CVS Impulse generation Cardiotonic Agents Chronotropic agents Alter the excitability of Pacemaker Conducting system Positive chronotropic agents Lead to increase in heart rate Negative chronotropic agents Lead to decrease in the heart rate 8-Dec-18 CVS Impulse generation

CVS Impulse generation Cardiotonic Agents Inotropic agents Affect the contractility of the cardiac muscles Positive inotropic agents Lead to increase in contraction Negative inotropic agents Lead to decrease in contraction 8-Dec-18 CVS Impulse generation

CVS Impulse generation Effects of Ions Calcium ions Have a positive inotropic effect  In ECF Ca++ concentration leads to  In force of contraction of cardiac muscle More Ca++ available for troponin  In ECF Ca++ concentration reduces Myocardial force of contraction 8-Dec-18 CVS Impulse generation

CVS Impulse generation Effects of Ions Calcium ions Have a chronotropic effect too  In ECF Ca++ concentration Slow the heart rate By elevating the excitation threshold 8-Dec-18 CVS Impulse generation

CVS Impulse generation Effects of Ions  In ECF Ca++ concentration Increases the heart rate Due to increase in rate of diastolic depolarization Purkinje cells are more sensitive to Ca++ Leads to development of ectopic foci 8-Dec-18 CVS Impulse generation

CVS Impulse generation Effects of Ions Sodium ions Have little effects under normal conditions A decrease in ECF Na+ concentration Slows the heart Decrease in amplitude of AP Severe reduction (10%) in Na+ concentration Leads to complete loss of excitability 8-Dec-18 CVS Impulse generation

CVS Impulse generation Effects of Ions Potassium ions An increase in ECF K+ concentration Dilated heart which is flaccid Heart rate falls Impaired conduction in AVNode Lead to atrial block 8-Dec-18 CVS Impulse generation

CVS Impulse generation Effects of Ions An increase in ECF K+ concentration Causes partial depolarization Shortens duration of AP Decreases amplitude & intensity of AP Hence the contraction of heart Becomes progressively weaker 8-Dec-18 CVS Impulse generation

Effects of Autonomic Nervous System Sympathetic stimulation increases Rate of sinus node discharge Rate of conduction Level of excitability of myocardium Force of contraction of myocardium 8-Dec-18 CVS Impulse generation

CVS Impulse generation Nor adrenalin Nor adrenalin increases The rate of SAN cells depolarization The rate of spontaneous discharge Heart rate 8-Dec-18 CVS Impulse generation

Effect of Nor Adrenalin Ca++ Nor adrenalin acts on 1 receptors Increase in cAMP Activated protein kinase A 1 receptor Adenyl cyclase GS protein ATP cAMP Protein Kinase Ca++ Ca++ Sarcoplasmic Ret Troponin 8-Dec-18 CVS Impulse generation

Effect of Nor Adrenalin Ca++ Protein Kinase A facillitates Opens long lasting Ca++ channels Influx of Ca++ into myocardial cell Leads to increase in strength of contraction 1 receptor Adenyl cyclase GS protein ATP cAMP Protein Kinase Ca++ Ca++ Sarcoplasmic Ret Troponin 8-Dec-18 CVS Impulse generation

CVS Impulse generation Parasympathetic Parasympathetic stimulation Causes release of Acetylcholine This causes a decrease Heart rate Excitability of AVN Slows transmission of impulses to ventricles 8-Dec-18 CVS Impulse generation

CVS Impulse generation Parasympathetic Very strong stimulation Can stop SAN discharge Block AVN transmission Ventricle can stop contraction Vagal escape Ectopic pacemaker from Purkinje fibers take over 8-Dec-18 CVS Impulse generation

CVS Impulse generation Parasympathetic Acetylcholine Activate M2 (muscarinic) receptors Through G-protein Open special K+ channels Efflux of K+ Hyperpolarization 8-Dec-18 CVS Impulse generation

CVS Impulse generation Parasympathetic Activation of M2 recptors also Decrease cAMP concentration in cell Slows opening of Ca++ channels Rate of diastolic depolarization is retarded It takes longer to reach threshold Heart rate is slowed 8-Dec-18 CVS Impulse generation

CVS Impulse generation Cardiac Glycosides Digitalis increase cardiac contractility Inhibits sodium-potassium ATPase In the heart myocardium There is an antiport transport mechanism 2Na+ 1 Ca++ 2Na+ 1 Ca++ Na+/K+ ATPase pump 2 K+ Ca++/Na++ antiport pump 3 Na+ 8-Dec-18 CVS Impulse generation

CVS Impulse generation Cardiac Glycosides Cell membrane exchange ICF calcium for ECF sodium 1 Ca++ for 2 Na+ The rate of exchange Proportional to concentration of Na+ in ICF 2Na+ 1 Ca++ 2Na+ 1 Ca++ Na+/K+ ATPase pump 2 K+ Ca++/Na++ antiport pump 3 Na+ 8-Dec-18 CVS Impulse generation

CVS Impulse generation Cardiac Glycosides Inhibition of Na+ - K+ pump Leads to increase in Na+ concentration in ICF This interferes with antiport mechanism 2Na+ 1 Ca++ 2Na+ 1 Ca++ Na+/K+ ATPase pump 2 K+ Ca++/Na++ antiport pump 3 Na+ 8-Dec-18 CVS Impulse generation

CVS Impulse generation Cardiac Glycosides There is increase in ca++ concentration in ICF Followed by  force of contraction of myocardial cells 2Na+ 1 Ca++ 2Na+ 1 Ca++ Na+/K+ ATPase pump 2 K+ Ca++/Na++ antiport pump 3 Na+ 8-Dec-18 CVS Impulse generation