cGMP facilitates calcium current via cGMP-dependent protein kinase in isolated rabbit ventricular myocytes.
The effect of guanosine 3',5'-cyclic monophosphate (cGMP) on L-type Ca current (ICa) was investigated in a study of rabbit ventricular myocytes using the whole-cell patch-clamp technique. Intracellular application of cGMP (100 MUm) increased ICa in the absence of isoprenaline or forskolin. 8-Bromo-cGMP (100 muM) and 8-(4-chlorophenylthio)-cGMP (8-pCPT-cGMP, 400 muM), relatively specific stimulators of cGMP-dependent protein kinase (cGMP-PK), also increased ICa. The stimulatory effect of 8-pCPT-cGMP was suppressed by Rp-8-chlorophenylthio-cGMP (400 muM), a phosphodiesterase-resistant cGMP-PK inhibitor. When ICa was increased by bath application of the non-specific phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX, 100 muM), 8-pCPT-cGMP (400 muM) resulted in additional stimulation of ICa. In the presence of 8-pCPT-cGMP, additional applications of isoprenaline (1 muM) or forskolin (1 muM) induced a further increase in ICa. From these results, it could be concluded that the activation of cGMP-dependent protein kinase is involved in the facilitation of ICa by cGMP in rabbit ventricular myocytes.
Han
J
J
Department of Physiology and Biophysics, Inje University, Pusan, 614-735 Korea.
Kim
E
E
Lee
S H
SH
Yoo
S
S
Ho
W K
WK
Earm
Y E
YE
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D013873:Thionucleotides / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D013873:Thionucleotides; D005576:Colforsin; C016276:8-bromocyclic GMP; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D011494:Protein Kinases; D006152:Cyclic GMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine