Cardiac myocytes and the cardiac action potential

Kenneth T. MacLeod, Steven B. Marston, Philip A. Poole-Wilson, Nicholas J. Severs and Peter H. Sugden

in Oxford Textbook of Medicine

Fifth edition

Published on behalf of Oxford University Press

Published in print May 2010 | ISBN: 9780199204854
Published online May 2010 | e-ISBN: 9780199570973 | DOI:

Series: Oxford Textbooks

Cardiac myocytes and the cardiac action potential

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Functional anatomy of the cardiac myocyte

Cardiac myocytes are the contractile cells of the heart and constitute the bulk of heart mass. There are differences between the myocytes of the ventricles, the atria, and the conduction system: ventricular myocytes are elongated cells and packed with myofibrils (the contractile apparatus) and mitochondria (for ATP production).

The myofibrils are repeating units (sarcomeres) made up of thin actin filaments anchored at the Z discs at either end of the sarcomere, and thick myosin filaments which interdigitate and interact with the thin filaments. Contraction results from sarcomere shortening produced by the ATP-dependent movement of the thin and thick filaments relative to one another. Atrial myocytes are long and slender, and differ in some of the features of ventricular myocytes. For example, transverse tubules (T-tubules) which are involved in entry of Ca2+ into the ventricular myocyte are essentially absent but there are more caveolae. Myocytes of the conduction system are small cells that possess only a rudimentary myofibrillar structure.

Myocytes are attached to their neighbours and to the extracellular matrix to allow transmission of force. At some regions of contact (the intercalated discs), specialized structures (the gap junctions) contain channels which form contiguous electrical connections between a myocyte and its neighbours, and allow passage of ions and small molecules.

Cardiac action potential

There is a potential difference (the membrane potential) across the plasma membrane such that the inside of the cell is negative compared to the outside by about 80 mV. This is caused largely by the efflux of K+ from the cell through K+ channels and down its concentration gradient until the electronegative force retaining K+ in the cell balances the tendency for efflux.

The sarcoplasmic reticulum (SR) is a lace-like membranous structure that surrounds the myofibrils and is a reservoir of the Ca2+ which participates in myofibrillar contraction. The plasma membrane of the ventricular myocyte contains deep, finger-like indentations (the T-tubules) that abut with the SR at junctional regions in register with the Z discs of the superficial sarcomeres.

When a myocyte is electrically excited, Na+ channels open and Na+ enters the cell down its own concentration gradient, thus producing an inward current and depolarizing the cell towards its equilibrium potential. This represents the initial phase (phase 0) of the action potential. As the myocyte depolarizes, the l-type Ca2+ channels in the T-tubules and plasma membrane open and Ca2+ enters the cell down its concentration gradient. The Na+ channels close rapidly, but the l-type Ca2+ channels remain open for longer and produce further depolarization. This is followed by phases 1 and 2 of the action potential where the tendency to depolarize is balanced by repolarizing outward current flow carried by a variety of K+ channels. The membrane potential in phase 2 is relatively stable and hence this phase is also known as the plateau phase.

The entry of Ca2+ in close apposition to the junctional SR causes the SR Ca2+-release channels to open, discharging about half of the SR Ca2+ reservoir into the cytoplasm in a process known as Ca2+-induced Ca2+-release. This increase in Ca2+ concentration (the Ca2+ transient) is sensed by a Ca2+-binding protein (troponin C) that is a component of the thin filament regulatory complex (the troponin–tropomyosin complex). This initiates myofibrillar contraction, which starts about halfway though phase 2.

As the l-type Ca2+ channels close, outward current flow though K+ channels predominates and the myocyte repolarizes towards the K+ equilibrium potential (phase 3). Ca2+ is removed from the cytoplasm and returned to the SR in an ATP-requiring process mediated by the sarcoplasmic/endoplasmic Ca2+ ATPase (SERCA2). Ca2+ is also expelled from the cell by the plasma membrane Na+,Ca2+ exchanger, which is electrogenic (three Na+ exchanged for one Ca2+) and tends to prolong the plateau phase. The behaviour of the Na+,Ca2+ exchanger is complex because—depending on the Na+ and Ca2+ concentrations and the membrane potential—it can reverse, thus mediating Ca2+ entry and repolarization. This occurs at depolarized potentials, and more so when intracellular Na+ is increased. In phase 4, repolarization is complete and the myocyte is electrically quiescent until the next depolarization.

Cardiac pacemaker and regulation of contractility

The ‘pacemaker’ or sinoatrial node contains myocytes that exhibit a different form of action potential from the ventricular myocytes because of differences in the expression of ion channels. The Na+ channel is essentially absent and depolarization is mediated by Ca2+ channels. The cell depolarizes spontaneously and gradually during phase 4 until the Ca2+ channels open and an action potential is produced. This partly results from the presence of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels which are absent from ventricular myocytes and which carry an inward-depolarizing Na+ current. The stimulus is then transmitted in a controlled manner via the conduction system to all regions of the heart.

Cardiac contractility is controlled largely by the sympathoadrenal system and the parasympathetic nervous system. β-Adrenergic stimulation increases the tendency of the l-type Ca2+ channel to open (positive inotropism). β-Stimulation also increases relaxation (positive lusitropism) by stimulation of SERCA2 and an increased rate of release of Ca2+ from the troponin complex. The positive chronotropic effects of β-stimulation result from increased HCN channel opening, causing an increased frequency of pacemaker depolarization. These effects are all opposed by the (cholinergic) muscarinic receptors of the parasympathetic nervous system.

Chapter.  10524 words.  Illustrated.

Subjects: Cardiovascular Medicine

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