Ca2+ channels involved in endothelin-induced mitogenic response in carotid artery vascular smooth muscle cells

• Published in: American Journal of Physiology: Cell Physiology 2002-02, Vol.282 (2), p.C330
• Main Authors: Kawanabe, Yoshifumi, Hashimoto, Nobuo, Masaki, Tomoh
• Format: Article
• Language: English
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00227.2001

Departments of 1  Neurosurgery and 2  Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8507, Japan Endothelin (ET)-1 activates two types of Ca 2+ -permeable nonselective cation channels (NSCC-1 and NSCC-2) and a store-operated Ca 2+ channel (SOCC) in rabbit internal carotid artery (ICA) vascular smooth muscle cells (VSMCs) in addition to the voltage-operated Ca 2+ channel (VOCC). These channels can be discriminated using the Ca 2+ channel blockers SK&F-96365 and LOE-908. SK&F-96365 is sensitive to NSCC-2 and SOCC, and LOE-908 is sensitive to NSCC-1 and NSCC-2. On the basis of sensitivity to nifedipine, a specific blocker of the L-type VOCC, VOCCs have a minor role in ET-1-induced mitogenesis. Both LOE-908 and SK&F-96365 inhibited ET-1-induced mitogenesis in a concentration-dependent manner, and the combination of LOE-908 and SK&F-96365 abolished it. The IC 50 values of these blockers for ET-1-induced mitogenesis correlated well with those of the ET-1-induced intracellular free Ca 2+ concentration responses. These results indicate that the inhibitory action of these blockers on ET-1-induced mitogenesis may be mediated by blockade of NSCC-1, NSCC-2, and SOCC. Collectively, extracellular Ca 2+ influx through NSCC-1, NSCC-2, and SOCC may be essential for ET-1-induced mitogenesis in ICA VSMCs. endothelin; calcium ion channel; cell proliferation