Received for publication August 11, 2004.
Revised November 9, 2004.
Accepted for publication November 9, 2004.

Inhibition of L-type Ca_v1.2 Ca²⁺ channels by LY294002 and Go6983

Abstract

Phosphatidylinositol 3-Kinase (PI3-K) is involved in physiological processes of cellular proliferation and inflammation, and, as postulated recently, in the regulation of L-type Ca²⁺ channels. The latter conclusion arose in part from the inhibitory action of the compound LY294002 which has been established as a selective PI3-K inhibitor (IC₅₀ of 1.4 µM). Herein, we show, however, that LY294002 and, in addition, an inhibitor of protein kinase C (PKC), Go6983, act as direct Ca²⁺ channel inhibitors with IC50 values of about 20 and 10 µM, respectively. Since both drugs are commonly used at concentrations of about 10 µM or higher, the interpretation of such experiments is questionable with respect to a regulatory action of PI3-K or PKC on L-type Ca²⁺ channels.

Key words: Muscarinic cholinergic, Calcium (Votage-Gated Channels), Protein Kinase C, Func. analysis receptor/ion channel mutants, Knockout