Ca2+ channels activated by endothelin-1 in CHO cells expressing endothelin-A or endothelin-B receptors

Departments of 1 Pharmacology, 2 Neurosurgery, and 3 Anesthesiology, Kyoto University Faculty of Medicine, Kyoto 606-8507, Japan We compared the Ca 2+ channels activated by endothelin-1 (ET-1) in Chinese hamster ovary (CHO) cells stably expressing endothelin type A (ET A ) or endothelin type B (ET B ) receptors using the Ca 2+ channel blockers LOE-908 and SK&F-96365. In both CHO-ET A and CHO-ET B , ET-1 at 0.1 nM activated the Ca 2+ -permeable nonselective cation channel-1 (NSCC-1), which was sensitive to LOE-908 and resistant to SK&F-96365. ET-1 at 1 nM activated NSCC-2 in addition to NSCC-1; NSCC-2 was sensitive to both LOE-908 and SK&F-96365. ET-1 at 10 nM activated the same channels as 1 nM ET-1 in both cell types, but in CHO-ET A , it additionally activated the store-operated Ca 2+ channel (SOCC), which was resistant to LOE-908 and sensitive to SK&F-96365. Up to 1 nM ET-1, the level of the formation of inositol phosphates (IPs) was low and similar in both cell types, but, at 10 nM ET-1, it was far greater in CHO-ET A than in CHO-ET B . These results show that, in CHO-ET A and CHO-ET B , ET-1 up to 10 nM activated the same Ca 2+ entry channels: 0.1 nM ET-1 activated NSCC-1, and ET-1 1 nM activated NSCC-1 and NSCC-2. Notably, in CHO-ET A , 10 nM ET-1 activated SOCCs because of the higher formation of IPs. endothelin-1; endothelin receptor; calcium channel; calcium ion; Chinese hamster ovary