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Cardiac alternans and intracellular calcium cycling
Author(s) -
Edwards Joshua N,
Blatter Lothar A
Publication year - 2014
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12231
Subject(s) - depolarization , contraction (grammar) , beat (acoustics) , calcium , biophysics , ventricular action potential , cardiac action potential , membrane potential , medicine , cardiology , intracellular , cardiac muscle , chemistry , cardiac cycle , calcium in biology , electrophysiology , repolarization , physics , biology , biochemistry , acoustics
Summary Cardiac alternans refers to a condition in which there is a periodic beat‐to‐beat oscillation in electrical activity and the strength of cardiac muscle contraction at a constant heart rate. Clinically, cardiac alternans occurs in settings that are typical for cardiac arrhythmias and has been causally linked to these conditions. At the cellular level, alternans is defined as beat‐to‐beat alternations in contraction amplitude (mechanical alternans), action potential duration ( APD ; electrical or APD alternans) and Ca 2+ transient amplitude (Ca 2+ alternans). The cause of alternans is multifactorial; however, alternans always originate from disturbances of the bidirectional coupling between membrane voltage (V m ) and intracellular calcium ([Ca 2+ ] i ). Bidirectional coupling refers to the fact that, in cardiac cells, V m depolarization and the generation of action potentials cause the elevation of [Ca 2+ ] i that is required for contraction (a process referred to as excitation–contraction coupling); conversely, changes of [Ca 2+ ] i control V m because important membrane currents are Ca 2+ dependent. Evidence is mounting that alternans is ultimately caused by disturbances of cellular Ca 2+ signalling. Herein we review how two key factors of cardiac cellular Ca 2+ cycling, namely the release of Ca 2+ from internal stores and the capability of clearing the cytosol from Ca 2+ after each beat, determine the conditions under which alternans occurs. The contributions from key Ca 2+ ‐handling proteins (i.e. surface membrane channels, ion pumps and transporters and internal Ca 2+ release channels) are discussed.