Ca2+-calmodulin Mediated Modulation of the Electrical Coupling of Ventricular Myocytes Isolated from Guinea Pig Heart

The mechanism for the regulation of junctional conductance (gi) by Ca2+ was examined in paired ventricular myocytes isolated from guinea pig heart. One cell of the pair was voltage-clamped by a single-patch pipette, and gi was measured after perforation of the non-junctional membrane of the partner cell. The average value of gi under control condition of pCa 9.0 was 181 ± 13 nS (n = 30). An elevation of calcium concentration ([Ca2+]i) in the intracellular perfusate from pCa 9.0 to pCa 5.7 resulted in a decrease of 32 ± 5% in gi (n = 18). In myocytes pretreated with W7 (10-4 M), a similar elevation of [Ca2+]i caused a decrease of only 10 ± 3% in gi (n = 6), indicating a protective action of W7 against Ca2+-mediated electrical uncoupling. W5 (10-4 M), a non-chlorinated derivative of W7, did not show such a protective action. Calmodulin (10-5 M) had no effects on gi at pCa 9.0. However, at moderately elevated [Ca2]i condition at pCa 7.0, calmodulin (10-5 M) decreased gi by 29 ± 6% (n = 4). These results suggest that calmodulin may play an important role in the Ca2+-mediated regulation of gap junctional channel function in the cardiac ventricular cells.