Inhibition of L-type Cav1.2 Ca2+ channels by 2,(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) and 2-[1-(3-dimethyl-aminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl) maleimide (Go6983)

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 2,(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), which has been established as a selective PI3-K inhibitor (IC50 = 1.4 muM). Herein we show, however, that LY294002 and an inhibitor of protein kinase C (PKC), 2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl) maleimide (Go6983), act as direct Ca2+-channel inhibitors, with IC50 values of approximately 20 and 10 muM, respectively. Because both drugs are commonly used at concentrations of approximately 10 muM 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.