Modulation of ATP-sensitive potassium channels by cGMP-dependent protein kinase in rabbit ventricular myocytes.
This investigation used a patch clamp technique to test the hypothesis that protein kinase G (PKG) contributes to the phosphorylation and activation of ATP-sensitive K(+) (K(ATP)) channels in rabbit ventricular myocytes. Nitric oxide donors and PKG activators facilitated pinacidil-induced K(ATP) channel activities in a concentration-dependent manner, and a selective PKG inhibitor abrogated these effects. In contrast, neither a selective protein kinase A (PKA) activator nor inhibitor had any effect on K(ATP) channels at concentrations up to 100 and 10 microm, respectively. Exogenous PKG, in the presence of both cGMP and ATP, increased channel activity, while the catalytic subunit 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 Mg(2+) from the internal solution, applying a PKG inhibitor, 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 regulated by a PKG-signaling pathway that acts via PKG-dependent phosphorylation. This mechanism may, at least in part, contribute to a signaling pathway that induces ischemic preconditioning in rabbit ventricular myocytes.
Han
J
J
Department of Physiology and Biophysics, College of Medicine, Inje University, Busan, 614-735, Korea.
Kim
N
N
Kim
E
E
Ho
W K
WK
Earm
Y E
YE
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010766:Phosphorylation; D015221:Potassium Channels / Q000378:metabolism*; D011817:Rabbits
D020030:Nitric Oxide Donors; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D017869:Cyclic GMP-Dependent Protein Kinases