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-γ (IFN-γ) on calcium movement in rat ventricular myocytes. L-type Ca²⁺ currents (I_Ca,L) were recorded with the whole-cell configuration of the patch-clamp techniques. IFN-γ induces current density reduction at the test potential of 0 mV 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,L amplitude decrease of about 46 ± 5.6%. The addition of IFN-γ to heparin-treated cells has no effect on I_Ca,L. Ryanodine induced an I_Ca,L current amplitude decrease of 35.1 ± 6.2%. The addition of IFN-γ to ryanodine-treated cells caused an additional I_Ca,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,L amplitudes. Subsequent addition of IFN-γ inhibited I_Ca,L for an additional 16.3 ± 4.4%. The employment of chelerythrine in this study prevented IFN-γ-induced L-type Ca²⁺ channel inhibition in only 10 min from the start of perfusion. Proposed mechanisms of regulation involved IFN-γ-induced IP3-sensitive Ca²⁺ release probably by a Ca²⁺-dependent translocation of from the cytoplasm to the cell membrane as the obligatory first step of the IFN-γ-induced L-type Ca²⁺ channel inhibition.

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