Sarcolemmal α2-adrenoceptors control protective cardiomyocyte-delimited sympathoadrenal response.

Autor: Kokoz YM; Institute of Theoretical and Experimental Biophysics, Russian Academy of Science, Institutskaya 3, Pushchino, Moscow Region 142290, Russia. Electronic address: yuryikokoz@gmail.com., Evdokimovskii EV; Institute of Theoretical and Experimental Biophysics, Russian Academy of Science, Institutskaya 3, Pushchino, Moscow Region 142290, Russia. Electronic address: onletaet@gmail.com., Maltsev AV; Institute of Theoretical and Experimental Biophysics, Russian Academy of Science, Institutskaya 3, Pushchino, Moscow Region 142290, Russia. Electronic address: goicr@rambler.ru., Nenov MN; Institute of Theoretical and Experimental Biophysics, Russian Academy of Science, Institutskaya 3, Pushchino, Moscow Region 142290, Russia; Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: mnnenov@utmb.edu., Nakipova OV; Institute of Cell Biophysics, Russian Academy of Sciences, Institutskaya 3, Pushchino, Moscow Region 142290, Russia. Electronic address: olga.nakipova@gmail.com., Averin AS; Institute of Cell Biophysics, Russian Academy of Sciences, Institutskaya 3, Pushchino, Moscow Region 142290, Russia. Electronic address: averinas82@gmail.com., Pimenov OY; Institute of Theoretical and Experimental Biophysics, Russian Academy of Science, Institutskaya 3, Pushchino, Moscow Region 142290, Russia. Electronic address: poleg237@rambler.ru., Teplov IY; Institute of Cell Biophysics, Russian Academy of Sciences, Institutskaya 3, Pushchino, Moscow Region 142290, Russia. Electronic address: T.I.Y@mail.ru., Berezhnov AV; Institute of Cell Biophysics, Russian Academy of Sciences, Institutskaya 3, Pushchino, Moscow Region 142290, Russia. Electronic address: g_56@rambler.ru., Reyes S; Division of Cardiovascular Diseases, Department of Molecular Pharmacology and Experimental Therapeutics, Stabile 5, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA. Electronic address: reyesramirez.santiago@mayo.edu., Alekseev AE; Division of Cardiovascular Diseases, Department of Molecular Pharmacology and Experimental Therapeutics, Stabile 5, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA. Electronic address: alekseev.alexey@mayo.edu.
Jazyk: angličtina
Zdroj: Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2016 Nov; Vol. 100, pp. 9-20. Date of Electronic Publication: 2016 Sep 19.
DOI: 10.1016/j.yjmcc.2016.09.006
Abstrakt: Sustained cardiac adrenergic stimulation has been implicated in the development of heart failure and ventricular dysrhythmia. Conventionally, α2 adrenoceptors (α2-AR) have been assigned to a sympathetic short-loop feedback aimed at attenuating catecholamine release. We have recently revealed the expression of α2-AR in the sarcolemma of cardiomyocytes and identified the ability of α2-AR signaling to suppress spontaneous Ca 2+ transients through nitric oxide (NO) dependent pathways. Herein, patch-clamp measurements and serine/threonine phosphatase assay revealed that, in isolated rat cardiomyocytes, activation of α2-AR suppressed L-type Ca 2+ current (I CaL ) via stimulation of NO synthesis and protein kinase G- (PKG) dependent activation of phosphatase reactions, counteracting isoproterenol-induced β-adrenergic activation. Under stimulation with norepinephrine (NE), an agonist of β- and α-adrenoceptors, the α2-AR antagonist yohimbine substantially elevated I CaL at NE levels >10nM. Concomitantly, yohimbine potentiated triggered intracellular Ca 2+ dynamics and contractility of cardiac papillary muscles. Therefore, in addition to the α2-AR-mediated feedback suppression of sympathetic and adrenal catecholamine release, α2-AR in cardiomyocytes can govern a previously unrecognized local cardiomyocyte-delimited stress-reactive signaling pathway. We suggest that such aberrant α2-AR signaling may contribute to the development of cardiomyopathy under sustained sympathetic drive. Indeed, in cardiomyocytes of spontaneously hypertensive rats (SHR), an established model of cardiac hypertrophy, α2-AR signaling was dramatically reduced despite increased α2-AR mRNA levels compared to normal cardiomyocytes. Thus, targeting α2-AR signaling mechanisms in cardiomyocytes may find implications in medical strategies against maladaptive cardiac remodeling associated with chronic sympathoadrenal stimulation.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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