Ca(2+)-calmodulin mediated modulation of the electrical coupling of ventricular myocytes isolated from guinea pig...

The mechanism for the regulation of junctional conductance (gj) 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 gj was measured after perforation of the non-junctional membrane of the partner cell. The average value of gj under control condition at 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 gj (n = 18). In myocytes pretreated with W7 (10(-4) M), a similar elevation of [Ca2+]i caused a decrease of only 10 +/- 3% in gj (n = 6), indicating a protective action of W7 against Ca(2+)-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 gj at pCa 9.0. However, at moderately elevated [Ca2+]i condition at pCa 7.0, calmodulin (10(-5) M) decreased gj by 29 +/- 6% (n = 4). These results suggest that calmodulin may play an important role in the Ca(2+)-mediated regulation of gap junctional channel function in the cardiac ventricular cells.