Pacemaker Vs Non Pacemaker Cells

PACEMAKER VS NON PACEMAKER CELLS Non-pacemaker The heart muscle cells - Atrial myocytes, ventricular myocytes and Purkinje cells are examples of nonpacemaker action potentials in the heart. Because these action potentials undergo very rapid depolarization, they are sometimes referred to as "fast response" action potentials. Non-pacemaker cells have a true resting membrane potential (phase 4) that remains near the equilibrium potential for K+ (EK) at – 90mV. When these cells (the myocytes) are rapidly depolarized to a threshold voltage of about - 70 mV (e.g., by an action potential in an adjacent connected cell), there is a rapid depolarization (phase 0) that is caused by a transient increase in fast Na+-channel conductance (gNa+) through fast sodium channels. At the same time sodium channels open, gK+ and outward directed K+ currents fall as potassium channels close. These two conductance changes move the membrane potential away from EK (which is negative) and closer toward the equilibrium potential for sodium (ENa), which is positive. Then L-type Ca++ channels open (phase 1 and 2), and this starts muscle contraction. Pacemaker Cells within the sinoatrial (SA) node are the primary pacemaker site within the heart. These cells have no true resting stable potential (4), but instead generate regular, spontaneous action potentials (opening of L type Ca++ channels). The depolarizing current is carried into the cell primarily by relatively slow Ca++ currents (first T, then L type) (4) instead of by fast Na+ currents (as in non-pacemakers cells). There are no fast Na+ channels and currents operating in SA nodal cells. Therefore, these pacemaker action potentials are sometimes referred to as "slow response" action potentials At the end of repolarization (-60 mV), ion channels open that conduct slow, inward (depolarizing) Na+ currents (funny currents). These depolarizing currents cause the membrane potential to begin to slowly depolarize, thereby initiating Phase 4. As the membrane potential reaches about -50 mV, transient or T-type Ca++ channel open. As Ca++ enters the cell through these channels, the inward directed Ca++ currents further depolarize the cell. As the membrane continues to depolarize to about -40 mV, the so-called long-lasting, or L- type Ca++ channels open. Opening of these channels causes more Ca++ to enter the cell and to further depolarize the cell until an action potential threshold is reached (usually -35 mV). The time to reach the threshold determines the heart rate – time between heartbeats. Activation The heart is a functional syncytium (a large cell-like structure formed by the joining together of two or more cells). In a functional syncytium, electrical impulses propagate freely between cells in every direction, so that the myocardium functions as a single contractile unit. Microscopically, the wave of depolarization propagates to adjacent cells via gap junctions located on the intercalated disk. This is the reason why the pacemaker call are able to depolarize the non-pacemaker cells. Gap junctions The wave of depolarization propagates to adjacent cells via gap junctions. Gap junctions determine how much depolarizing current passes from excited to non-excited regions of the network. Intrinsic automaticity of the heart The heart will beat independently of any nervous or hormonal influences. This spontaneous rhythm of the heart (called intrinsic automaticity) can be altered by nervous impulses or by circulatory substances, like adrenaline – DRUG TARGETS. Each cell in the heart will spontaneously contract at a regular rate because the cell spontaneously "depolarises". Muscle fibres from different parts of the heart have different rates of spontaneous depolarisation; the cells from the ventricle are the slowest, and those from the atria are faster. The coordinated contraction of the heart is produced because the cells with the fastest rate of depolarisation "capture" the rest of the heart muscle cells. These cells with the fastest rate of depolarisation are in the sinoatrial node (SA node), the "pacemaker" of the heart. Sequential activation • SA node → atria → AV node → Bundle of His → right and left bundle branches → apex → Purkinje fibres → transmission of APs through ventricular wall → ventricular contraction Sinus node • Generates normal rhythmic impulse • Small, flat strip of cardiac muscle 3mm wide, 15mm long and 1mm thick • Located in superior posterolateral wall of RA (below and lateral to SVC opening) • Spontaneously changing potentials initiate APs that spread to atrial myocytes Internodal • Anterior, middle and posterior pathways • Conduct from sinus node → atrioventricular node AV node • Impulse from atria is delayed here before passing into ventricles • Posterior wall of RA behind tricuspid valve AV Bundle of His • Conducts from atria → ventricles Left and right • Conducts to ventricles branches of • Become continuous with cardiac muscle fibres Purkinje fibres • Rapid transmission: high permeability of gap junctions between cells in the fibres