CA2-CALMODULIN MEDIATED MODULATION OF THE ELECTRICAL COUPLING OF VENTRICULAR MYOCYTES ISOLATED FROM GUINEA-PIG HEART()

The mechanism for the regulation of junctional conductance (g(j)) by C a2+ was examined in paired ventricular myocytes isolated from guinea p ig heart. One cell of the pair was voltage-clamped by a single-patch p ipette, and g(j) was measured after perforation of the non-junctional membrane of the partner cell. The average value of g(j) under control condition at pCa 9.0 was 181 +/- 13 nS (n = 30). An elevation of calci um concentration ([Ca2+](i)) in the intracellular perfusate from pCa 9 .0 to pCa 5.7 resulted in a decrease of 32 +/- 5% in g(j) (n = 18). In myocytes pretreated with W7 (10(-4) M), a similar elevation of [Ca2+] (i) caused a decrease of only 10 +/- 3% in g(j) (n = 6), indicating a protective action of W7 against Ca2+-mediated electrical uncoupling. W 5 (10(-4) M), a non-chlorinated derivative of W7, did not show such a protective action. Calmodulin (10(-5) M) had no effects on g(j) at pCa 9.0. However, at moderately elevated [Ca2+](i) condition at pCa 7.0, calmodulin (10(-5)M) decreased g(j) by 29 +/- 6% (n=4). These results suggest that calmodulin may play an important role in the Ca2+-mediate d regulation of gap junctional channel function in the cardiac Ventric ular cells.