Endothelin-1-induced contraction of rat thoracic aorta depends on calcium entry through three types of calcium channel

We have recently shown that endothelin-1 (ET-1) activates two types of Ca2-penneable nonselective cation channels (designated NSCC-1 and NSCC-2) and store-operated Ca2+ channel (SOCC). These channels can be pharmacologically discriminated using 1-{beta-[3-(4-methoxyphenyl)propoxyl-4-methuxyphenethy l}-1-H-imidazoel hydrouhloride (SK&F 96365) (a blocker of NSCC-2 and SOCC) and (RS)-(3,4-dihydro-6,7-diInethoxyisoquinoline-1-gamma1)-2-phenyl-N,N-di- [2-(2,3,4-trimethoxypheny])ethyl]acetamide (LOE 908) (a blocker of NSCC-1 a nd NSCC-2). For our study we characterized Ca2+ channels involved in ET-1-i nduced contractions and increases in the intracellular free Ca2+ concentrat ion ([Ca2+]i) using these blockers. Our results show that the response to l ower concentrations of ET-1 involves only one Ca2+ channel which is sensiti ve to SK&F 96365 and LOE 908 (NSCC-2). In contrast. the response to higher concentrations of ET-1 involves two types of Ca2+ channel in addition to NS CC-2: one is sensitive to SK&F 96365 but resistant to LOE 908 (SOCC), and t he other is resistant to SK&F 96365 but sensitive to LOE 908 (NSCC-1). Furt hermore, the percentage contribution of Ca2+ entry through NSCC-1, NSCC-2 a nd SOCC is calculated to be 10%, 50-60% and 30-40%, respectively.