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

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

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3 Scopus citations

Abstract

Mechanisms of the regulation of voltage-dependent L-type Ca2+ channels that function in mammalian cardiocytes with the participation of the system of cyclic nucleotides have been studied. It was shown that in the presence of arginine (1 mM) in all experimental media, activation of cGMP-dependent phosphorylation leads to the suppression of the amplitude of basal L-type Ca2+ currents in cardiomyocytes of rat ventricles. The effect of the compounds regulating the activity of different signal molecules of the NO-cGMP cascade on L-type Ca2+ currents was studied. It was shown that the addition of 5 mM arginine, an endogenous source of NO, or 1 mM nitroprusside (SNP), an exogenous source of NO, decreases the amplitude of the current by 30 ± 10%. The non-specific blocker of NO synthases 7NI abolishes the effect of arginine. The blocker of soluble guanylyl cyclase ODQ (50 μ) also eliminates the effect of arginine and SNP. The inhibitory effect of arginine, SNP, and 8Br-cGMP disappeared in the presence of the blocker of protein kinase G KT5823 (0.5 μ), which directly indicates that the effect of these compounds is related to the activation of PKG-dependent phosphorylation. The L-type Ca2+ current could also decrease due to an increase in the activity of phosphodiesterase II. However, in the presence of the selective blocker of this phosphodiesterase EHNA (30 μ), the inhibitory action of both arginine and SNP on the current persisted. The L-type Ca2+ current activated by isoproterenol (0.1 μ) is only partially blocked by acetylcholine (0.1 mM). The agonists of the NO-cGMP cascade arginine and SNP, as well as 8Br-cGMP, as distinct from their effect on basal currents, practically do not affect isoproterenol-activated currents. However, acetylcholine applied in combination with the agonists of the NO-cGMP cascade completely inhibits isoproterenol-induced currents to the basal level.

Original languageEnglish (US)
Pages (from-to)377-387
Number of pages11
JournalBiologicheskie Membrany
Volume25
Issue number5
StatePublished - Dec 5 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Grushin, K. S., Nenov, M. N., Dynnik, V. V., Semushina, S. G., Pakhomova, I. A., Murashev, A. N., & Kokoz, Y. M. (2008). Role of the NO-cGMP cascade in the regulation of L-type Ca2+ current in isolated cardiomyocytes. Biologicheskie Membrany, 25(5), 377-387.