Roscovitine inhibits CaV3.1 (T-type) channels by preferentially affecting closed-state inactivation.

ABSTRACT: T-type calcium channels (Ca(V)3) play an important role in many physiological and pathological processes, including cancerogenesis. Ca(V)3 channel blockers have been proposed as potential cancer treatments. Roscovitine, a trisubstituted purine, is a cyclin-dependent kinase (CDK) inhibitor that is currently undergoing phase II clinical trials as an anticancer drug and has been shown to affect calcium and potassium channel activity. Here, we investigate the effect of roscovitine on Ca(V)3.1 channels. Ca(V)3.1 channels were transiently expressed in human embryonic kidney 293 cells, and currents were recorded by using the whole-cell patch-clamp technique. Roscovitine blocks Ca(V)3.1 channels with higher affinity for depolarized cells (EC₅₀ of 10 μM), which is associated with a negative shift i

SUBMITTER: Yarotskyy V 

PROVIDER: S-EPMC3263959 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature