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1 We have recently shown that endothelin-1 (ET-1) activates two types of Ca 2+ -permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and store-operated Ca 2+ channel (SOCC). These channels can be pharmacologically discriminated using Ca 2+ channel blockers such as SK&F 96365 and LOE 908. Here we characterized Ca 2+ entry channels involved in ET-1-induced contractions of rat thoracic aortic rings and increases in the intracellular free Ca 2+ concentration ([Ca 2+ ] i ) of single smooth muscle cells using these blockers. 2 LOE 908 or a blocker of voltage-operated Ca 2+ channel nifedipine had no e ect on the contractions and increases in [Ca 2+ ] i induced by thapsigargin or ionomycin, whereas SK&F 96365 abolished them. 3 The contractions and increases in [Ca 2+ ] i induced by ET-1 depended on extracellular Ca 2+ but were resistant to nifedipine. The responses to lower concentrations (40.1 nM) of ET-1 were abolished by either SK&F 96365 or LOE 908. The responses to higher concentrations (51 nM) were abolished by SK&F 96365, but were partially resistant to LOE 908. 4 SK&F 96365 inhibited the LOE 908-resistant contractions induced by higher concentrations of ET-1 with IC 50 values similar to those for contractions induced by thapsigargin or ionomycin. 5 These results show that the contractions and increases in [Ca 2+ ] i of rat aortic smooth muscles at lower concentrations of ET-1 involve only one Ca 2+ entry channel which is sensitive to SK&F 96365 and LOE 908 (NSCC-2), whereas those at higher concentrations of ET-1 involve another Ca 2+ entry channel which is sensitive to SK&F 96365 but resistant to LOE 908 (SOCC) in addition to the former channel.

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1 In A7r5 cells loaded with the Ca 2+ indicator fura-2, we examined the e ect of a Ca 2+ channel blocker SK&F 96365 on increases in intracellular free Ca 2+ concentrations ([Ca 2+ ]i) and Mn 2+ quenching of fura-2¯uorescence by endothelin-1 (ET-1). Whole-cell patch-clamp was also performed.