| Autor: |
Yu, Liangzhu, Li, Mincai, She, Tonghui, Shi, Chunrong, Meng, Wei, Wang, Banghua, Cheng, Menglin |
| Předmět: |
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| Zdroj: |
Journal of Membrane Biology; Apr2013, Vol. 246 Issue 4, p343-353, 11p |
| Abstrakt: |
The cardiac L-type Ca channel current ( I) 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 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 density without altering its voltage dependence of activation and inactivation. In line with the absence of functional changes, ET-1 increased L-type Ca channel pore-forming α-subunit mRNA and protein levels without affecting the mRNA expression of auxiliary β- and α/δ-subunits. Furthermore, an actinomycin D chase experiment revealed that ET-1 did not alter α-subunit mRNA stability. These effects of ET-1 were inhibited by the ET receptor antagonist BQ-123 but not the ET receptor antagonist BQ-788. Moreover, the effects of ET-1 on I and α-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 Ca channel in cardiomyocytes via activation of ERK1/2 through the ET receptor, which may contribute to the electrical remodeling of heart during postnatal development and cardiac hypertrophy. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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