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

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Abstract

The main goal of the present work was to study the mechanisms of regulation of voltage-gated L-type Ca2+ currents 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. Selective antagonists of α2-adrenoceptors(α2-ARs) yohimbine and rauwolscine did not interfere with the effect of agmatine. In contrast,efaroxan and idazoxan,which are known to antagonize both α2-ARs and type 1 imidazoline receptors(I1Rs),decreased the efficiency of agmatine almost twofold. The inhibitor of NO-synthase 7NI insignificantly influenced the suppressive action of agmatine on L-type Ca2+ currents,whereas the inhibitor of protein kinase C 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 activation of endothelial NO-synthase(eNOS) followed by cGMP-dependent inhibition of the L-type Ca2+ current. Most likely,agmatine acts via I1Rs coupled to a signaling pathway involving activation of protein kinase C. Consistently,we showed that single cardiomyocytes express nischarin gene,which is considered in the modern literature as the major candidate for the gene encoding I1Rs. To our knowledge,this is the first demonstration of the I1Rs expression at the level of individual cells,including cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)307-316
Number of pages10
JournalBiologicheskie Membrany
Volume29
Issue number5
StatePublished - Dec 1 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Maltsev, A. V., Evdokimovskii, E. V., Pimenov, O. Y., Nenov, M. N., & Kokoz, Y. M. (2012). Regulation of potential-dependent L-type Ca2+ currents by agmatine. Imidazoline receptors in isolated cardiomyocytes. Biologicheskie Membrany, 29(5), 307-316.