Ca2+ Entry Channels in Rat Thoracic Aortic Smooth Muscle Cells Activated by Endothelin-1

The Japanese Journal of Pharmacology

Taijiro Enoki³  Makoto Okazawa²  Xiao-Feng Zhang²  Yasushi Iwamuro¹  Tomoh Masaki⁴  Soichi Miwa²  Yasuo Okamoto² 

[1] Department of Neurosurgery, Kyoto University Faculty of Medicine;Department of Pharmacology, Kyoto University Faculty of Medicine;Department of Anesthesiology, Kyoto University Faculty of Medicine;National Cardiovascular Center Reseach Institute

关键词: Endothelin;    Vascular smooth muscle cell;    Ca2+ channel;    LOE 908;    SK&F 96365;   

DOI  :  10.1254/jjp.80.281

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(52)Cited-By(14)The contraction of the rat aorta induced by endothelin-1 (ET-1) requires entry of extracellur Ca2+, but involvement of voltage-operated Ca2+ channel is minor. Using whole-cell recordings of patch-clamp and monitoring of the intracellular free Ca2+ concentration ([Ca2+]i), we characterized Ca2+ entry channels in A7r5 cells activated by ET-1. ET-1 activates three types of voltage-independent Ca2+ entry channels: two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca2+ channel (SOCC). Furthermore, it was found that these channels can be pharmacologically discriminated using Ca2+ channel blockers such as SK&F 96365 and LOE 908. NSCC-1 is resistant to SK&F 96365, but sensitive to LOE 908, whereas NSCC-2 is sensitive to both SK&F 96365 and LOE 908. SOCC is sensitive to SK&F 96365, but resistant to LOE 908. Using these channel blockers, we analyzed Ca2+ entry channels involved in the ET-1-induced contractions of rat thoracic aorta and increases in [Ca2+]i of single smooth muscle cells. The responses to lower concentrations of ET-1 (≤0.1 nM) were abolished by either SK&F 96365 or LOE 908 alone. In contrast, the responses to higher concentrations of ET-1 (≥1 nM) were suppressed by SK&F 96365 or LOE 908 to about 10% and 35% of controls, respectively, and abolished by combined treatment with SK&F 96365 and LOE 980. These results show that the responses of rat aorta to lower concentrations of ET-1 involve only one Ca2+ channel that is sensitive to SK&F 96365 and LOE 908 (NSCC-2), whereas those to higher concentrations of ET-1 involve NSCC-1, NSCC-2 and SOCC, contributing 10%, 55% and 35%, respectively, to total Ca2+ entry.

【 授权许可】

Unknown