Role of the NO-cGMP cascade in regulation of L-type Ca2+ currents in isolated cardiomyocytes

K. S. Grushin, M. N. Nenov, V. V. Dynnik, S. G. Semushina, I. A. Pakhomova, A. N. Murashev, Yu M. Kokoz

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Regulatory mechanisms of voltage-dependent L-type Ca2+ channels involving the cyclic nucleotide system of mammalian cardiomyocytes have been studied. Activation of cGMP-dependent phosphorylation in the presence of 1 mM arginine in all experimental media resulted in inhibition of amplitudes of basal L-type Ca2+ currents in rat ventricular myocytes. Effects of compounds regulating the activity of different compoments of the NO-cGMP cascade on L-type Ca2+ currents were investigated. It was found that endogenous (arginine, 5 mM) and exogenous (sodium nitroprusside, 1 mM) NO sources decreased the Ca2+ current amplitude by 30 ± 10%. The nonspecific NO synthase blocker 7NI (2μM) abolished the effect of arginine, while the soluble guanylyl cyclase blocker ODQ (50 μM) eliminated the effects of both arginine and sodium nitroprusside. The fact that inhibitory effects of arginine, sodium nitroprusside and 8Br-cGMP disappeared in the presence of the protein kinase G blocker KT5823 (0.5, 1 μM) provides direct evidence in favor of activating effect of these compounds on PKG-dependent phosphorylation. Inhibition of L-type Ca2+ currents can also be due to activation of phosphodiesterase II. However, the selective phosphodiesterase II blocker EHNA (30 μM) failed to abolish inhibitory effects of arginine and sodium nitroprusside on Ca2+ currents. Isoproterenol (0.1 μM)-activated L-type Ca2+ currents were only partly blocked by acetylcholine (0.1 mM). Contrary to basal currents, the NO-cGMP cascade agonists arginine and sodium nitroprusside (SNP), like 8Br-cGMP, had no effect on isoproterenol-induced currents. Full inhibition of isoproterenol-induced currents was achieved through combination of acetylcholine with NO-cGMP cascade agonists.

Original languageEnglish (US)
Pages (from-to)243-252
Number of pages10
JournalBiochemistry (Moscow) Supplement Series A: Membrane and Cell Biology
Issue number3
StatePublished - Sep 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology


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