The inhibitory effect of BIM (I) on L-type Ca²⁺ channels in rat ventricular cells.
We investigated the effect of a specific protein kinase C (PKC) inhibitor, bisindolylmaleimide I [BIM (I)], on L-type Ca(2+) channels in rat ventricular myocytes. BIM (I) alone inhibited the L-type Ca(2+) current in a concentration-dependent manner, with a K(d) value of 3.31 ± 0.25 μM, 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 3μ 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 Ca(2+) current or on the inhibitory effect of BIM (I) on the L-type Ca(2+) current. The results suggest that the inhibitory effect of BIM (I) on the L-type Ca(2+) 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.
Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Republic of Korea.
Youn Kyoung
YK
Son
Da Hye
DH
Hong
Tae-Hoon
TH
Choi
Seong Woo
SW
Choi
Dong Hoon
DH
Shin
Sung Joon
SJ
Kim
In Duk
ID
Jung
Yeong-Min
YM
Park
Won-Kyo
WK
Jung
Dae-Joong
DJ
Kim
Il-Whan
IW
Choi
Won Sun
WS
Park
D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000166:cytology* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008301:Maleimides / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D020746:Calcium Channels, L-Type; D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C; C070515:bisindolylmaleimide I