J. Han et al., Modulation of ATP-sensitive potassium channels by cGMP-dependent protein kinase in rabbit ventricular myocytes, J BIOL CHEM, 276(25), 2001, pp. 22140-22147
This investigation used a patch clamp technique to test the hypothesis that
protein kinase G (PKG) contributes to the phosphorylation and activation o
f ATP-sensitive K+ (K-ATP) channels in rabbit ventricular myocytes. Nitric
oxide donors and PKG; activators facilitated pinacidil-induced K-ATP channe
l activities in a concentration-dependent manner, and a selective PKG inhib
itor abrogated these effects. In contrast, neither a selective protein kina
se A (PKA) activator nor inhibitor had any effect on K-ATP channels at conc
entrations up to 100 and 10 muM, respectively. Exogenous PKG, in the presen
ce of both cGMP and ATP, increased channel activity, while the catalytic su
bunit of PKA had no effect. PKG activity was prevented by heat inactivation
, replacing ATP with adenosine 5 ' -O-(thiotriphosphate) (a nonhydrolyzable
analog of ATP), removing Mg2+ from the internal solution, applying a PKG i
nhibitor, or by adding exogenous protein phosphatase 2A The effects of cGMP
analogs and PKG were observed under conditions in which PKA was repressed
by a selective PKA inhibitor. The results suggest that K-ATP channels are r
egulated by a PKG-signaling pathway that acts via PKG-dependent phosphoryla
tion. This mechanism may, at least in part, contribute to a signaling pathw
ay that induces ischemic preconditioning in rabbit ventricular myocytes.