Endothelin-1 and insulin activate the steady-state voltage dependent R-type Ca super(2+) channel in aortic smooth muscle cells via a pertussis toxin and cholera toxin sensitive G-protein

• Published in: Molecular and cellular biochemistry 1998-06, Vol.183 (1-2), p.39-47
• Main Authors: Bkaily, Ghassan, Naik, Radha, Jaalouk, Doris, Jacques, Danielle, Economos, Demetri, D'Orleans-Juste, Pedro, Pothier, Pierre
• Format: Article
• Language: English
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1023/A:1006887714302

In single rabbit aortic smooth muscle cells, and at a concentration known to induce a maximum sustained increase of intracellular Ca super(2+) via activation of the steady-state voltage dependent R-type Ca super(2+) channels, endothelin-1 (10 super(-7) M) and insulin (80 kU/ml) were found to induce a sustained increase in cytosolic free Ca super(2+) ([Ca] sub(i)) levels that was significantly attenuated by pre-treatment with either pertussis toxin (PTX), cholera toxin (CTX) or removal of extracellular Ca super(2+). However, both PTX and CTX failed to inhibit the sustained depolarization-evoked sustained Ca super(2+) influx and [Ca] sub(i) elevation via activation of the R-type Ca super(2+) channels. Moreover, ET-1 and insulin-evoked sustained increases in Ca super(2+) influx were not attenuated by the selective PKC inhibitor, bisindolylmaleimide (BIS), or the specific L-type Ca super(2+) channel blocker, nifedipine, but were completely reversed by the R-type Ca super(2+) channel blocker, (-) PN 200-110 (isradipine). These data suggest that both insulin and ET-1 activate the nifedipine-insensitive but isradipine-sensitive steady state voltage dependent R-type Ca super(2+) channels present on rabbit VSMCs and these channels are directly coupled to PTX and CTX sensitive G protein(s).