Endothelin-1 Stimulates the Expression of L-Type Ca2+ Channels in Neonatal Rat Cardiomyocytes via the Extracellular Signal–Regulated Kinase 1/2 Pathway

Endothelin-1 Stimulates the Expression of L-Type Ca2+ Channels in Neonatal Rat Cardiomyocytes via... The cardiac L-type Ca2+ channel current (I Ca,L) plays an important role in controlling both cardiac excitability and excitation–contraction coupling and is involved in the electrical remodeling during postnatal heart development and cardiac hypertrophy. However, the possible role of endothelin-1 (ET-1) in the electrical remodeling of postnatal and diseased hearts remains unclear. Therefore, the present study was designed to investigate the transcriptional regulation of I Ca,L mediated by ET-1 in neonatal rat ventricular myocytes using the whole-cell patch-clamp technique, quantitative RT-PCR and Western blotting. Furthermore, we determined whether the extracellular signal–regulated kinase 1/2 (ERK1/2) pathway is involved. ET-1 increased I Ca,L density without altering its voltage dependence of activation and inactivation. In line with the absence of functional changes, ET-1 increased L-type Ca2+ channel pore-forming α1C-subunit mRNA and protein levels without affecting the mRNA expression of auxiliary β- and α2/δ-subunits. Furthermore, an actinomycin D chase experiment revealed that ET-1 did not alter α1C-subunit mRNA stability. These effects of ET-1 were inhibited by the ETA receptor antagonist BQ-123 but not the ETB receptor antagonist BQ-788. Moreover, the effects of ET-1 on I Ca,L and α1C-subunit expression were abolished by the ERK1/2 inhibitor (PD98059) but not by the p38 MAPK inhibitor (SB203580) or the c-Jun N-terminal kinase inhibitor (SP600125). These findings indicate that ET-1 increased the transcription of L-type Ca2+ channel in cardiomyocytes via activation of ERK1/2 through the ETA receptor, which may contribute to the electrical remodeling of heart during postnatal development and cardiac hypertrophy. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Endothelin-1 Stimulates the Expression of L-Type Ca2+ Channels in Neonatal Rat Cardiomyocytes via the Extracellular Signal–Regulated Kinase 1/2 Pathway

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Publisher
Springer-Verlag
Copyright
Copyright © 2013 by Springer Science+Business Media New York
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-013-9538-7
Publisher site
See Article on Publisher Site

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