Opposite effects of angiotensin II and the protein kinase C activator OAG on cardiac Na+ channels.

Elementary Na+ currents were recorded at 19 degrees C in cell-attached and inside-out patch-clamp experiments to study the influence of the vasoactive peptide angiotensin II (A II) and of the diacylglycerol analogue OAG (1-oleoyl-2-acetyl-sn-glycerol) on open probability and gating properties of single cardiac Na+ channels from cultured neonatal rat cardiocytes. Treating the cardiocytes with A II caused Na+ channel activation: reconstructed peak INa increased to 137 +/- 17.5% of control at 3 mumol/liters and to 176 +/- 42% at 30 mumol/liter. This NPo increase developed without major changes in open state and burst activity, even at 30 mumol/liter. OAG (6 mumol/liter) did not mimic this A II action. By contrast, OAG treatment of the cardiocytes had the opposite effect on NPo and diminished reconstructed peak INa to 67 +/- 4.9% of the control. The putative protein kinase C inhibitor staurosporine (0.2 mumol/liter) abolished this INa depression and led to a normalization of NPo. OAG had the same effect on isolated Na+ channels. Exposure of the cytoplasmic surface of inside-out patches to 1 mumol/liter OAG reversibly depressed, in the simultaneous presence of 50 mumol/liter Mg-ATP, the reconstructed peak INa to 40 +/- 9.7% of the control but left unit, tau open and burst activity unaffected. No NPo depression was obtained in the absence of Mg-ATP indicating that Mg-ATP may serve as phosphate donor. Obviously, after phosphorylation by protein kinase C, cardiac Na+ channels attain a reduced open probability but appear to preserve their kinetic properties.(ABSTRACT TRUNCATED AT 250 WORDS)