Abstract 17427: A Unique “Cellular Fibrillation” Status in Mouse Ventricular Myocytes
Different intracellular calcium (Cai) wave patterns have been observed in cardiac myocytes. However, their mechanisms and corresponding electrophysiological properties remain unclear. In the present study, we have generated various patterns of Cai waves in isolated mouse ventricular myocytes under highly-activated Cai cycling states, such as high external Ca concentration or in the present of -adrenergic stimulation (i.e. isoproterenol and Bay K8644). Our results revealed at least three distinct types of Ca wave dynamics: I) slow propagating planar waves; II) Repetitive single spiral waves; III) Multiple spiral/micro waves, in which average Cai level remained high. All waves were completely blocked by tetracaine (1 mM), suggesting RyR leaking is the original source for the waves. Simultaneous recording of membrane potential under current-clamp mode revealed that these complex Cai wave dynamics have several functional consequences. The cell exhibited individual or oscillatory EADs and/or DADs under the conditions with type I or type II Cai waves. Interestingly, a unique “cellular fibrillation” status was associated with type III Cai waves. Under this condition, the cell maintained a high Cai level and a depolarized membrane potential (~ -20 mV) and thus lost its excitability and contractility. We also found that in the same cell, the Ca waves can be converted from one type to another by changing the Ca handling conditions. The multiple spiral/micro waves (type III) were transformed into slow-propagating, planar waves (type I) by a Ca/Na-free Tyrode's solution or by Gadolinium (Gd3+), a nonselective TRPC channel blocker; but not by nifedipine (L-type Ca channel blocker), SEA0400 (Na-Ca exchange blocker) or TTX (Na channel blocker). Hyperpolarizing the cell membrane by external injection of an outward current also transformed type III to type I Ca waves, suggesting the facilitating role of membrane current in the generation of the cellular fibrillation status. Termination of the cellular fibrillation by blocking TRPC channel activity may provide new opportunities for the treatment of clinical ventricular fibrillation.
- © 2011 by American Heart Association, Inc.