An outwardly rectifying Cl- current, ICl,swell, is activated by swelling and mechanical stretch of cardiac myocytes and has emerged as an important regulator of cardiac function in both physiologic and pathophysiologic situations. ICl,swell modulates cardiac electrical activity, myocyte volume regulation, apoptosis, and perhaps ischemic preconditioning. This current also is chronically activated under isosmotic conditions in myocytes isolated from ischemic models and non-ischemic models of heart failure, indicating a role in cardiac pathology. The regulation of ICl,swell by signaling cascades is complex. The current is controlled by PKC, PKA, and PTK and their respective phosphatases. In addition, ICl,swell is governed by autocrine-paracrine factors including angiotensin II, EGF, and endothelin and by reactive oxygen species produced by sarcolemmal NAD(P)H oxidase and perhaps other sources. Here we review the characteristics of cardiac ICl,swell, its regulation by signaling cascades, and the implications of ICl,swell for cardiac function.
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