Arylbenzazepines are potent modulators for the delayed rectifier K+ channel: a potential mechanism for their neuroprotective effects.

ABSTRACT: (+/-) SKF83959, like many other arylbenzazepines, elicits powerful neuroprotection in vitro and in vivo. The neuroprotective action of the compound was found to partially depend on its D(1)-like dopamine receptor agonistic activity. The precise mechanism for the (+/-) SKF83959-mediated neuroprotection remains elusive. We report here that (+/-) SKF83959 is a potent blocker for delayed rectifier K(+) channel. (+/-) SKF83959 inhibited the delayed rectifier K(+) current (I(K)) dose-dependently in rat hippocampal neurons. The IC(50) value for inhibition of I(K) was 41.9+/-2.3 microM (Hill coefficient = 1.81+/-0.13, n = 6), whereas that for inhibition of I(A) was 307.9+/-38.5 microM (Hill coefficient = 1.37+/-0.08, n = 6). Thus, (+/-) SKF83959 is 7.3-fold more potent in suppressing I(K) than I(A

SUBMITTER: Chen XQ 

PROVIDER: S-EPMC2690691 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature