Regulation of the calcium slow channel by cyclic GMP dependent protein kinase in chick heart cells.
In order to assess the interaction between the cAMP-dependent and the cGMP-dependent phosphorylation pathways on the slow Ca2+ current (ICa(L)), whole-cell voltage-clamp experiments were conducted on embryonic chick heart cells. Addition of 8Br-cGMP to the bath solution reduced the basal (unstimulated) ICa(L). Intracellular application of the catalytic subunit of PK-A (PK-A(cat); 1.5 microM) via the patch pipette rapidly potentiated ICa(L) by 215 +/- 16%) (n = 4); subsequent addition of 1 mM 8Br-cGMP to the bath reduced the amplitude of ICa(L) towards the initial control values (123 +/- 29%). Intracellular application of PK-G (25 nM pre-activated by 10(-7) M cGMP), rapidly inhibited the basal ICa(L) by 64 +/- 6% (n = 8). Heat-denatured PK-G was ineffective. Subsequent additions of relatively high concentrations of 8Br-cAMP (1 mM) or isoproterenol (ISO, 1-10 microM) did not significantly remove the PK-G blockade of ICa(L). The results of the present study suggest that: (a) 8Br-cGMP can inhibit the basal or stimulated (by PK-A(cat)) ICa(L) in embryonic chick myocardial cells. (b) PK-G applied intracellularly inhibits the basal ICa(L).
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D006352:Heart Ventricles; D009206:Myocardium / Q000201:enzymology*; D018408:Patch-Clamp Techniques; D015398:Signal Transduction / Q000502:physiology*
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; C016276:8-bromocyclic GMP; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D002118:Calcium