The inhibitory effect of BIM (I) on L-type Ca<SUP>2+</SUP> channels in rat ventricular cells

초록

We investigated the effect of a specific protein kinase C (PKC) inhibitor, bisindolylmaleimide I [BIM (I)], on L-type Ca2+ channels in rat ventricular myocytes. BIM (I) alone inhibited the L-type Ca2+ current in a concentration-dependent manner, with a K-d value of 3.31 +/- 0.25 mu M, and a Hill coefficient of 2.34 +/- 0.23. Inhibition was immediate after applying BIM (I) in the bath solution and then it partially washed out. The steady-state activation curve was not altered by applying 3 mu M BIM (I), but the steady-state inactivation curve shifted to a more negative potential with a change in the slope factor. Other PKC inhibitors, PKC-IP and chelerythrine, showed no significant effects either on the L-type Ca2+ current or on the inhibitory effect of BIM (I) on the L-type Ca2+. current. The results suggest that the inhibitory effect of BIM (I) on the L-type Ca2+ current is independent of the PKC pathway. Thus, our results should be considered in studies using BIM (I) to inhibit PKC activity and ion channel modulation. (C) 2012 Elsevier Inc. All rights reserved.

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