Physiology of the Heart Conduction System Cardiac Cellular Electrophysiology Assoc. Prof. MUDr. Markéta Bébarová, PhD Department of Physiology Faculty of Medicine Masaryk University This presentation includes only the most  important terms and facts. Its content by  itself is not a sufficient source of information required to pass the Physiology exam.  ORGANIZATION OF CARDIOVASCULAR SYSTEM Roles of the Cardiovascular System • primary role ‐ distribution of dissolved gases and other nutrients • several secondary roles, for example: ‐ fast chemical signalling to the cells (circulating hormones and neurotransmitters) ‐ thermoregulation (delivery of heat from the core to the surface of the body) ‐ immune reaction • roles of the heart: ‐ primary role ‐ pumping of blood ‐ endocrinne organ (natriuretic peptides) ORGANIZATION OF CARDIOVASCULAR SYSTEM RIGHT  ATRIUM RIGHT  VENTRICLE LEFT  ATRIUM LEFT  VENTRICLE LUNGS PULMONARY  ARTERY PERIPHERAL ORGANS AORTA RIGHT HEART LEFT HEART TWO  PUMPS  INTERCONNECTED IN  SERIES SUPERIOR                    VENA  CAVA AORTA PULMONARY  ARTERY INFERIOR                    VENA  CAVA RIGHT  ATRIUM LEFT ATRIUM LEFT VENTRICLE RIGHT VENTRICLE RIGHT  ATRIUM AORTA PULMONARY  ARTERY SUPERIOR                    VENA  CAVA INFERIOR                    VENA  CAVA LEFT ATRIUM LEFT VENTRICLE RIGHT VENTRICLE ORGANIZATION OF CARDIOVASCULAR SYSTEM Two Main Phases of the Cardiac Cycle DIASTOLE PHASE OF   FILLING  of the ventricles SYSTOLE EJECTION  PHASE ONE WAY VALVES DIASTOLE SYSTOLE ATRIOVENTRICULAR (mitral and tricuspid) open closed SEMILUNAR (aortal and pulmonary) closed open ‐ mechanical connections ‐ electrical connections ‐ gap junctions ORGANIZATION OF CARDIOVASCULAR SYSTEM Two Major Types of Cardiac Cells • cardiomyocytes of the working myocardium ‐ specialized for contraction (atrial and ventricular myocytes) cell 1 cell 2 sarcomere FUNCTIONAL SYNCYTIUM ORGANIZATION OF CARDIOVASCULAR SYSTEM Two Major Types of Cardiac Cells • cardiomyocytes of the working myocardium ‐ specialized for contraction (atrial and ventricular myocytes) • cardiomyocytes of the cardiac conduction system ‐ specialized for: ‐ automatic excitation (pacemaker activity) ‐ conduction of excitation The cardiac conduction system ensures:  1) generation of automatic electrical activity of the heart (pacemaker activity) that initiates its mechanical activity 2) optimal timing of the mechanical activity of the heart as a  pump ECG CARDIAC CONDUCTION SYSTEM SA node atrial muscle  AV node bundle  branches bundle of His Purkinje fibres ventricular  muscle  HIERARCHY OF PACEMAKERS SA AV CARDIAC CONDUCTION SYSTEM SINOATRIAL (SA) NODE PRIMARY pacemaker (60‐100 impulses/min) 16  pacemaker  P cells are impaired, activity is slowed or stopped  transmission  of excitation from P cells to the atrial cells is  reduced or interrupted SICK SINUS SYNDROME basement  membrane myofibrils PACEMAKER P CELLS with intrinsic  automaticity TRANSITIONAL T CELLS gap junctions atrial myocardium CARDIAC CONDUCTION SYSTEM TWO TYPES of the SA‐nodal cells      SA node CARDIAC CONDUCTION SYSTEM SINOATRIAL (SA) NODE PRIMARY pacemaker (60‐100 impulses/min) ATRIOVENTRICULAR (AV) NODE SECONDARY pacemaker (40‐55 impulses/min) INTERNODAL PREFERENTIAL PATHWAYS N TRANSITIONAL ZONES AN ATRIO‐NODAL  ZONE NH NODE‐HIS  ZONE atrium internodal pathways NH AN HIS BUNDLE atrio‐ventricular  fibrous barrier CENTRAL  NODAL  CELLS THREE TYPES of the AV‐nodal cells      CARDIAC CONDUCTION SYSTEM AV node 18 SOLE PATHWAY FOR PROPAGATION OF EXCITATION FROM ATRIA  TO VENTRICLES (NH zone merges into the bundle of His) DELAY IN PROPAGATION OF EXCITATION, ~100 ms (important for adequate timing of atrial and ventricular contractions) SUBSTITUTIVE (SECONDARY) PACEMAKER (40‐55 impulses/min; importance in the case of sick sinus syndrome)  FILTER OF SUPRAVENTRICULAR  TACHYARRHYTHMIAS atrial excitations are transmitted to the ventricles only up to the  limited frequency 180‐200 excitations/min (the heart function  as a pump is preserved) CARDIAC CONDUCTION SYSTEM AV node CARDIAC CONDUCTION SYSTEM Conduction velocity in atrial and ventricular muscle: 1 m/s SINOATRIAL (SA) NODE PRIMARY pacemaker (60‐100 impulses/min) INTERNODAL PREFERENTIAL PATHWAYS 1 m/s ATRIOVENTRICULAR (AV) NODE SECONDARY pacemaker (40‐55 impulses/min) TERCIARY pacemaker (25‐40 impulses/min) PURKINJE FIBRES BUNDLE OF HIS BUNDLE BRANCHES (LEFT AND RIGHT) 0.05 m/s 1 m/s 1 m/s 4 m/s 0.05 m/s CARDIAC CELLULAR ELECTROPHYSIOLOGY Ionic Channels Movement of ions through the open channels down their electrochemical (concentration + electrical) gradients + - + - + - + - + - + - Na+ K+ Ca2+ resting membrane voltage EK 0 mV + _ ENa ECa Vm = i - e ie CARDIAC CELLULAR ELECTROPHYSIOLOGY Ionic Currents Underlying Action Potential Configuration SA node AV node atrial muscle  ventricular muscle  bundle of His bundle branches Purkinje fibres time CARDIAC CELLULAR ELECTROPHYSIOLOGY Ionic Currents Underlying Action Potential Configuration initial/fast  depolarization (equilibrium between depolarizing  and repolarizing currents) 0 mV 1 2 3 4 0 transpolarization _+ ‐80 mV early  repolarization plateau phase final/late repolarization resting membrane voltage (Emr) CARDIAC CELLULAR ELECTROPHYSIOLOGY Ionic Currents Underlying Action Potential Configuration Na+ repolarization INa depolarization threshold  voltage ICa ‐35 mV Ca2+ K+ Ito plateau ‐65 mV Vmr ENa ECa 0 mV + _ EK IK + IK1  100 ms many subtypes of potassium channels (currents) CARDIAC CELLULAR ELECTROPHYSIOLOGY Ionic Currents Underlying Action Potential Configuration INa OPEN STATE (depolarization over threshold voltage) ACTIVATION INACTIVATION (at maintained membrane depolarization) RESTING STATE (closed) inactivation  gate activation  gate INACTIVATED STATE (closed) CARDIAC CELLULAR ELECTROPHYSIOLOGY Mechanism of the initial fast depolarization (phase 0) regenerative (self restoring) process produced by POSITIVE FEEDBACK  between  MEMBRANE VOLTAGE  and CONDUCTANCE   of   MEMBRANE  CHANNELS (gNa, gCa)                depolarizing currents ↑ depolarization  ↑conductance of Na+ (Ca2+) channels  ↑ INa (ICa) (directly proportionate to the  fraction  of   Na+ (Ca2+) channels in the open state) INa ICa 0 working myocardium ‐ INa CARDIAC CELLULAR ELECTROPHYSIOLOGY Refractory Period – Suppression of Excitability RELATIVE ABSOLUTE contraction action potential protection of the heart against: retrograde propagation of excitation (reentry) tetanic contraction at higher heart rate CARDIAC CELLULAR ELECTROPHYSIOLOGY Refractory Period – Suppression of Excitability RELATIVE ABSOLUTE contraction action potential TECG VULNERABLE  PERIOD  (propagated  responses) increased  susceptibility to  ventricular  fibrillation !!! EFFECTIVE  REFRACTORY  PERIOD (ARP + period of  responses that do  not propagate) CLINICAL ASPECTS CARDIAC CELLULAR ELECTROPHYSIOLOGY Refractory Period ‐ Mechanism INa OPEN STATE (depolarization over threshold voltage) ACTIVATION INACTIVATION (at maintained membrane depolarization) INACTIVATED STATE (closed) RESTING STATE (closed) inactivation  gate activation  gate RECOVERY FROM  INACTIVATION  (at repolarization) ICa CARDIAC CELLULAR ELECTROPHYSIOLOGY Pacemaker Activity ‐ Mechanism CARDIAC CELLULAR ELECTROPHYSIOLOGY Pacemaker Activity ‐ Mechanism maximal  diastolic voltage threshold  voltage             ICa‐L FACTORS DETERMINING THE HEART RATE: 1) maximal diastolic voltage 2) steepness of diastolic depolarization 3) threshold voltage for activation of ICa-L CARDIAC CELLULAR ELECTROPHYSIOLOGY Pacemaker Activity ‐ Mechanism COMPLEX PROCESS resulting from an INTERPLAY between • REPOLARIZING CURRENTS, namely IK (including IK,Ach) • DEPOLARIZING CURRENTS, namely If, ICa-T, and INaCa maximal  diastolic voltage threshold  voltage             ICa‐T ICa‐L IK If INaCa INaCa CARDIAC CELLULAR ELECTROPHYSIOLOGY Pacemaker Activity ‐ Mechanism ICa‐T ICa‐L IK If SYMPATHETIC STIMULATION •  cAMP  If and ICa-T  rate of diastolic depolarization  threshold voltage for activation of ICa-L ( excitability)    CARDIAC CELLULAR ELECTROPHYSIOLOGY Pacemaker Activity ‐ Mechanism ICa‐T ICa‐L IK If PARASYMPATHETIC STIMULATION • activation of IK,Ach  maximal diastolic voltage  threshold voltage for activation of ICa-L ( excitability)  (IK,Ach) •  cAMP  If and ICa-T  rate of diastolic depolarization     ECG SPREADING OF EXCITATION IN THE HEART SA node atrial muscle  AV node bundle  branches bundle of His Purkinje fibres ventricular  muscle  +++++ +++++ ----- ----- +++++ +++++ ----- ----- electric field (magnitude, direction)