Research Topic

Ca2+ Signaling and Heart Rhythm

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Ca2+ has a key regulatory role as a ubiquitous second messenger in the intricate workings of the heart. In cardiac myocytes, Ca2+ signalling is involved in the control of electrophysiological function, excitation-contraction coupling, modulation of contractile function, energy balance, cell death, and gene ...

Ca2+ has a key regulatory role as a ubiquitous second messenger in the intricate workings of the heart. In cardiac myocytes, Ca2+ signalling is involved in the control of electrophysiological function, excitation-contraction coupling, modulation of contractile function, energy balance, cell death, and gene transcription. Furthermore, although such diverse Ca2+-dependent regulatory processes occur simultaneously in a cell, distinct signals can be resolved by local Ca2+ sensitive protein complexes and differential Ca signal integration.
Recent evidence indicates that in additional to the voltage dependent generation and regulation of sinoatrial node (SAN) automaticity, which involves cyclic activation and deactivation of membrane ion channels, including the hyperpolarization-activated current (If), the T-type (ICaT) and L-type (ICaL) Ca2+ currents, and delayed rectifier K+ current (IK), among others, a Ca2+ clock generated by rhythmic spontaneous sarcoplasmic reticular Ca2+ release also regulates sinoatrial node (SAN) automaticity. These highlight the complexity of cardiac pacemaker mechanisms through which cardiac rhythm is regulated on a beat-to-beat basis. Furthermore, regardless of mechanism, calcium is also likely to be involved in the ectopic cardiac rhythms that occur in both atrial or ventricular tissues through the generation of triggered activity often in the form of delayed afterdepolarizations, particularly following cellular Ca2+ overloading. Recent studies have also implicated it in Na+ channel expression with consequences for conduction velocity and therefore for arrhythmic substrate. At the cellular level, such regulation involves control of the activity of membrane ion channels and Ca2+ handling proteins, in turn involving multiple extra- and intracellular signalling pathways. In addition to its importance for normal heart function, such regulation also plays a crucial role in disease conditions.
This Focus Issue will provide a up-to-date review of the major progress concerning the role of Ca2+ in the electrophysiological function of the heart, that has been made over the past few decades, with a focus in its role in both normal and abnormal cardiac rhythm. These extend from these physiological roles of Ca2+ signalling in cardiac pacemaker function ranging from its involvement in generation of pacemaker potentials in the SAN to the pathological role of abnormalities in Ca2+ signalling in both atrial and ventricular arrhythmogenesis. It will also seek to bridge the gap between advances in basic science and the development of new therapies. We will compile and edit a coherant set of review articles and original research contributions from key opinion leaders in the field, and focus on the direct clinical implications of the basic science research now and in the future.


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