Physiology

Origin of the Heartbeat and electrical activity

Cardiac Muscle membrane potential The transmembrane action potential of single cardiac muscle cells is characterized by: o o o o o Phase 0 - Rapid depolarization Phase 1 -Initial rapid repolarization Phase 2 - Plateau Phase 3 - Slow repolarization process Phase 4 - Resting membrane potential

Initial depolarization: Na+ influx through rapidly opening Na+ channels (Na+ current, INa). Rapid repolarization phase - The inactivation of Na+ channels. Plateau phase - Ca2+ influx through more slowly opening Ca2+ channels (Ca2+ current, ICa), Repolarization - net K+ efflux through multiple types of K+ channels (refer to picture with
comparison)

Pacemaker membrane potential Rhythmically discharging cells have a membrane potential that, after each impulse, declines to the firing level - prepotential or pacemaker potential triggers the next impulse. At the peak of each impulse, IK begins - repolarization. IK then declines, and a channel that can pass both Na+ and K+ is activated. (Because this
channel is activated following hyperpolarization, it is referred to as an "h" channel)

As Ih increases, the membrane begins to depolarize, forming the first part of the prepotential. Ca2+ channels then open. o These are of two types in the heart, the T (for transient) channels and the L (for long-lasting) channels. o The calcium current (ICa) due to opening of T channels completes the prepotential, and ICa due to opening of L channels produces the impulse.
(refer to picture with comparison above)

Other ion channels are also involved, and there is evidence that local Ca2+ release from the sarcoplasmic reticulation (Ca2+sparks) occurs during the prepotential. The action potentials in the SA and AV nodes are largely due to Ca2+, with no contribution by Na+ influx - there is no sharp, rapid depolarizing spike before the plateau, as there is in other parts of the conduction system and the atrial and ventricular fibers. Prepotentials are normally prominent only in the SA and AV nodes P cells.

The characteristic rapid rising phase of the fast-response action potential is a result of a sudden increase in Na+ permeability. This produces what is referred to as the fast inward current of Na+ and causes the membrane potential to move rapidly toward the sodium equilibrium potential. As indicated in this period of very high sodium permeability (phase 0) is short-lived.7 Development and maintenance of a depolarized plateau state (phase 2) is accomplished by the interactions of at least three separate processes: (1) a sustained reduction in K+ permeability, (2) a slowly developed and sustained increase in the membrane's permeability to Ca2+, and (3) electrogenic action of an Na+/Ca2+ exchanger in which three Na+ ions move into the cell in exchange for a single Ca2+ ion moving out of the cell. The initial fast inward current is small (or even absent) in cells that have slow-response action potentials. The slow rising phase of these action potentials is therefore primarily a result of an inward movement of Ca2+ ions. In both types of cells, the membrane is repolarized (phase 3) to its original resting potential as the K+ permeability increases and the Ca2+ and Na+ permeabilities return to their low resting values. These late permeability changes produce what is referred to as the delayed outward current.

Cells B, C, and D are shown in the resting phase with more negative charges inside than outside. Cell A is shown in the plateau phase of an action potential and has more positive charges inside than outside. Because of the gap junctions, electrostatic attraction can cause a local current flow (ion movement) between the depolarized membrane of active cell A and the polarized membrane of resting cell B, as indicated by the arrows in the figure. This ion movement depolarizes the membrane of cell B. Once the local currents from active cell A depolarize the membrane of cell B near the gap junction to the threshold level, an action potential will be triggered at that site and will be conducted over cell B. Because cell B branches (a common morphological characteristic of cardiac muscle fibers), its action potential will evoke action potentials on cells C and D. This process is continued through the entire myocardium. Thus, an action potential initiated at any site in the myocardium will be conducted from cell to cell throughout the entire myocardium.

Cardiac muscle cells are connected by intercalated discs which contain: 1. Adherins: proteins that form firm mechanical junctions between adjacent cell membranes in desmosomes 2. Connexin: proteins that form channels within gap junctions - low-resistance electrical connections between adjacent cells

Conduction velocity The speed at which an action potential propagates through a region of cardiac tissue Varies considerably in different areas in the heart and is determined by three variables: i. directly dependent on the diameter of the muscle fiber involved e.g. conduction over small-diameter cells in the AV node is significantly slower than conduction over large-diameter cells in the ventricular Purkinje system. ii. directly dependent on the intensity of the local depolarizing currents, which are in turn directly determined by the rate of rise of the action potential. Rapid depolarization favours rapid conduction. iii. dependent on the capacitive and/or resistive properties of the cell membranes, gap junctions, and cytoplasm. Electrical characteristics of gap junctions can be influenced

by external conditions that promote phosphorylation/dephosphorylation of the connexin proteins. Control of heart rate

Autonomic Nervous system:

Alters the course of spontaneous depolarization of the resting potential in SA pacemaker cells. Autonomic fibers also influence the conduction velocity of action potentials through the heart. o These effects are most notable at the AV node and can influence the duration of the PR interval.

1. Sympathetic: Increases HR Norepinephrine Increase the inward currents carried by Na+ and by Ca2+ during the diastolic interval These changes will increase the HR by increasing the rate of diastolic depolarization Increases in sympathetic activity increase conduction velocity (positive dromotropic effect) 2. Parasympathetic: Decreases heart rate Vagus nerve

Acetylcholine o increases the permeability of the resting membrane to K+ and decreases the diastolic permeability to Na+ initial hyperpolarization of the resting membrane potential by bringing it closer to the K+ equilibrium potential slow the rate of spontaneous depolarization of the resting membrane. o Both of these effects increase the time between beats by prolonging the time required for the resting membrane to depolarize to the threshold level. There is normally some continuous tonic activity of cardiac parasympathetic nerves thus the normal resting heart rate is approximately 70 bpm Increases in parasympathetic activity decrease conduction velocity (have a negative dromotropic effect).

There are other factors that can alter the HR e.g. o An abnormally high concentration of Ca2+ in the extracellular fluid, tends to decrease the heart rate by shifting the threshold potential.

Spread of excitation

Depolarization initiated in the SA node spreads radially through the atria converges on the AV node. Atrial depolarization is complete in about 0.1 s. Because conduction in the AV node is slow, a delay of about 0.1 s (AV nodal delay) occurs before excitation spreads to the ventricles. It is interesting to note here that when there is a lack
of contribution of INa in the depolarization (phase 0) of the action potential, a marked loss of conduction is observed.

This delay is shortened by stimulation of the sympathetic nerves to the heart and lengthened by stimulation of the vagus. From the top of the septum, the wave of depolarization spreads in the rapidly conducting Purkinje fibers to all parts of the ventricles in 0.080.1 s. Depolarization of the ventricular muscle starts at the left side of the interventricular septum and moves first to the right across the mid portion of the septum. The wave of depolarization then spreads down the septum to the apex of the heart. It returns along the ventricular walls to the AV groove, proceeding from the endocardial to the epicardial surface.

Mechanical events of the cardiac cycle

Heart Sounds
Two sounds are normally heard through a stethoscope during each cardiac cycle. The first is a low, slightly prolonged "lub" (first sound), caused by vibrations set up by the sudden closure of the AV valves at the start of ventricular systole (Figure 313). The second is a shorter, high-pitched "dup"(second sound), caused by vibrations associated with closure of the aortic and pulmonary valves just after the end of ventricular systole. A soft, low-pitched third sound is heard about one third of the way through diastole in many normal young individuals. It coincides with the period of rapid ventricular filling and is probably due to vibrations set up by the inrush of blood. A fourth sound can sometimes be heard immediately before the first sound when atrial pressure is high or the ventricle is stiff in conditions such as ventricular hypertrophy. It is due to ventricular filling and is rarely heard in normal adults.

Cardiac Output : Volume of blood pumped by the heart each minute Stroke Volume: The volume of blood pumped out of a ventricle in one beat Contractility: Ability of heart to alter its contractile force and velocity independent of fiber length

CO = HR x SV (L/min)

Frank-Starling Law "energy of contraction is proportional to the initial length of the cardiac muscle fiber" The length of the muscle fibers (the extent of the preload) is proportional to the end-diastolic volume