L-type Ca2+ channels' involvement in IFN-γ-induced signaling in rat ventricular cardiomyocytes

The purpose of this study was to examine the effects of interferon- (IFN-) on calcium movement in rat ventricular myocytes. L-type Ca2+ currents (I-Ca,I-L) were recorded with the whole-cell configuration of the patch-clamp techniques. IFN- induces current density reduction at the test potential of 0mV by 47.6 +/- 7.4%. Heparin, a selective inhibitor of inositol-1,4,5-triphosphate (IP3)-induced Ca2+ release, applied via a patch pipette, induced an I-Ca,I-L amplitude decrease of about 46 +/- 5.6%. The addition of IFN- to heparin-treated cells has no effect on I-Ca,I-L. Ryanodine induced an I-Ca,I-L current amplitude decrease of 35.1 +/- 6.2%. The addition of IFN- to ryanodine-treated cells caused an additional I-Ca,I-L inhibiting of 17.6 +/- 4.8%. Both cyclopiazonic acid (CPA), a specific SERCA inhibitor, and a combination of CPA and ryanodine caused a significant reduction of the I-Ca,I-L amplitudes. Subsequent addition of IFN- inhibited I-Ca,I-L for an additional 16.3 +/- 4.4%. The employment of chelerythrine in this study prevented IFN--induced L-type Ca2+ channel inhibition in only 10min from the start of perfusion. Proposed mechanisms of regulation involved IFN--induced IP3-sensitive Ca2+ release probably by a Ca2+-dependent translocation of PKC from the cytoplasm to the cell membrane as the obligatory first step of the IFN--induced PKC-dependent L-type Ca2+ channel inhibition.