The Effect of Acute Hypoxia on Excitability in the Heart and the L-Type Calcium Channel as a Therapeutic Target

William   A.   Macdonald; Livia   C.   Hool

Abstract

Acute hypoxia is induced during coronary occlusion or when oxygen supply does not meet demand and can trigger cardiac arrhythmia. Cardiac ion channels shape the action potential and excitability of the heart. Acute hypoxia regulates the function of cardiac ion channels including the L-type Ca channel that is the main route for Ca influx into cardiac myocytes and shapes the plateau phase of the action potential. This article will review the evidence for alteration of ion channel function during hypoxia as a result of modification of thiol groups by reactive oxygen species. The effect of acute hypoxia on cardiac excitability will be examined and how this can lead to life threatening arrhythmias with particular reference to the L-type Ca channel. Recent evidence indicates the L-type channel is a suitable target for the development of drugs that can modify channel function during hypoxia or oxidative stress to prevent induction of arrhythmia or development of pathology.

Keywords: L-type Ca2+ channel, hypoxia, reactive oxygen species, redox, early afterdepolarizations, arrhythmias, anti-arrhythmic therapy