Regulation of potential-dependent L-type Ca2+ currents by agmatine. Imidazoline receptors in isolated cardiomyocytes

A. V. Maltsev, E. V. Evdokimovskii, O. Yu Pimenov, M. N. Nenov, Yu M. Kokoz

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The main goal of the present work was to study the mechanisms of voltage-gated L-type Ca2+ currents regulation by agmatine in isolated cardiomyocytes and to determine whether agmatine is involved in mediating the "arginine paradox". It was shown that agmatine at concentrations from 200 μM to 15 mM inhibited L-type Ca2+ currents in isolated cardiomyocytes in a dose-dependent manner. The selective antagonists of α2-adrenoceptors (α2-ARs), yohimbine and rauwolscine, did not modulate the effect of agmatine. In contrast, efaroxan and idazoxan known to antagonize both α2-ARs and type 1 imidazoline receptors (I1Rs) decreased the efficiency of agmatine almost twofold. The NO synthase inhibitor 7NI insignificantly influenced the suppressive action of agmatine on L-type Ca2+ currents, whereas the protein kinase C inhibitor, calphostin C, markedly reduced the effects of agmatine. Arginine did not affect L-type Ca2+ currents in the presence of agmatine and vice versa. These data suggest that agmatine is not involved in mediating the "arginine paradox" and that its effects are not due to the activation of endothelial NO synthase (eNOS) followed by cGMP-dependent inhibition of L-type Ca2+ current. Most likely, agmatine acts via I1Rs coupled with the signaling pathway that involves the activation of protein kinase C. Previously nothing was known about possible localization of I1Rs in isolated cardiomyocytes. Consistently, we have shown that single cardiomyocytes express the nischarin genes homologous to the IRAS gene, which is considered in the modern literature as the major candidate for the gene encoding I1Rs. To the best our knowledge, this is the first demonstration of I1Rs expression at the level of individual cells, including cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)279-287
Number of pages9
JournalBiochemistry (Moscow) Supplement Series A: Membrane and Cell Biology
Volume6
Issue number4
DOIs
StatePublished - Oct 1 2012

    Fingerprint

Keywords

  • Ca current
  • agmatine
  • imidazoline receptors

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this