title: ATP-sensitive K(+) channel activation by nitric oxide and protein kinase G in rabbit ventricular myocytes.
abstract: The present investigation tested the hypothesis that nitric oxide (NO) potentiates ATP-sensitive K(+) (K(ATP)) channels by protein kinase G (PKG)-dependent phosphorylation in rabbit ventricular myocytes with the use of patch-clamp techniques. Sodium nitroprusside (SNP; 1 mM) potentiated K(ATP) channel activity in cell-attached patches but failed to enhance the channel activity in either inside-out or outside-out patches. The 8-(4-chlorophenylthio)-cGMP Rp isomer (Rp-CPT-cGMP, 100 microM) suppressed the potentiating effect of SNP. 8-(4-Chlorophenylthio)-cGMP (8-pCPT-cGMP, 100 microM) increased K(ATP) channel activity in cell-attached patches. PKG (5 U/microl) added together with ATP and cGMP (100 microM each) directly to the intracellular surface increased the channel activity. Activation of K(ATP) channels was abolished by the replacement of ATP with ATPgammaS. Rp-pCPT-cGMP (100 microM) inhibited the effect of PKG. The heat-inactivated PKG had little effect on the K(ATP) channels. Protein phosphatase 2A (PP2A, 1 U/ml) reversed the PKG-mediated K(ATP) channel activation. With the use of 5 nM okadaic acid (a PP2A inhibitor), PP2A had no effect on the channel activity. These results suggest that the NO-cGMP-PKG pathway contributes to phosphorylation of K(ATP) channels in rabbit ventricular myocytes.
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, Inje University, Busan 614-735, Korea. phyhanj@ijnc.inje.ac.kr
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Hyun
authors.initials: H
authors.lastname: Joo
authors.forename: Euiyong
authors.initials: E
authors.lastname: Kim
authors.forename: Yung E
authors.initials: YE
authors.lastname: Earm
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D054648:Protein Phosphatase 2; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D015221:Potassium Channels; D013873:Thionucleotides; D009599:Nitroprusside; D009569:Nitric Oxide; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D000255:Adenosine Triphosphate; D017869:Cyclic GMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D006152:Cyclic GMP