Ca2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes.
Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with regulation of the L-type Ca2(+)-channel current (ICa) through the opposite actions of two second messengers, cyclic AMP and cyclic GMP. While cyclic AMP stimulation of ICa is mediated by the activation of cyclic AMP-dependent protein kinase, inhibition of ICa by cyclic GMP in frog heart is largely mediated by activation of cyclic AMP phosphodiesterase. The present patch-clamp study reveals that, in rat ventricular cells, cyclic GMP can also regulate ICa via activation of endogenous cyclic GMP-dependent protein kinase (cGMP-PK). Indeed, the effect of cyclic GMP on ICa was mimicked by intracellular perfusion with the proteolytic active fragment of purified cGMP-PK. Moreover, cGMP-PK immunoreactivity was detected in pure rat ventricular myocytes by using a specific polyclonal antibody. These results demonstrate a dual mechanism for the inhibitory action of cyclic GMP in heart, as well as a physiological role for cGMP-PK in the control of mammalian heart function.
Méry
P F
PF
Laboratoire de Physiologie Cellulaire Cardiaque, Institut National de la Santé et de la Recherche Médicale U-241, Université de Paris-Sud.
Lohmann
S M
SM
Walter
U
U
Fischmeister
R
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D006152:Cyclic GMP / Q000494:pharmacology*; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000201:enzymology; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology; D010446:Peptide Fragments / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D016276:Ventricular Function
D015220:Calcium Channels; D010446:Peptide Fragments; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine