Ca(2+) channels activated by endothelin-1 in CHO cells expressing endothelin-A or endothelin-B receptors.

Abstract

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 > or = 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.