Regulation of potential-dependent L-type Ca2+ currents by agmatine. Imidazoline receptors in isolated cardiomyocytes
The main goal of the present work was to study the mechanisms of voltage-gated L-type Ca 2+ 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...
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Veröffentlicht in: | Biochemistry (Moscow). Supplement series A, Membrane and cell biology Membrane and cell biology, 2012-10, Vol.6 (4), p.279-287 |
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Zusammenfassung: | The main goal of the present work was to study the mechanisms of voltage-gated L-type Ca
2+
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 Ca
2+
currents in isolated cardiomyocytes in a dose-dependent manner. The selective antagonists of α
2
-adrenoceptors (α
2
-ARs), yohimbine and rauwolscine, did not modulate the effect of agmatine. In contrast, efaroxan and idazoxan known to antagonize both α
2
-ARs and type 1 imidazoline receptors (I
1
Rs) decreased the efficiency of agmatine almost twofold. The NO synthase inhibitor 7NI insignificantly influenced the suppressive action of agmatine on L-type Ca
2+
currents, whereas the protein kinase C inhibitor, calphostin C, markedly reduced the effects of agmatine. Arginine did not affect L-type Ca
2+
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 Ca
2+
current. Most likely, agmatine acts via I
1
Rs coupled with the signaling pathway that involves the activation of protein kinase C. Previously nothing was known about possible localization of I
1
Rs 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 I
1
Rs. To the best our knowledge, this is the first demonstration of I
1
Rs expression at the level of individual cells, including cardiomyocytes. |
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ISSN: | 1990-7478 1990-7494 |
DOI: | 10.1134/S1990747812040058 |