Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701, Republic of Korea.
Life Sci. 2011 Aug 29;89(9-10):331-6. doi: 10.1016/j.lfs.2011.06.017. Epub 2011 Jul 7.
We investigated the effects of BMS-204352 (BMS), a big-conductance calcium-activated potassium (BK(Ca)) channel activator, on L-type Ca(2+) channels.
Electrophysiological recordings were performed in isolated rat ventricular myocytes. Whole-cell configuration was used.
BMS caused inhibition of the Ca(2+) current in a dose-dependent manner, with K(d) of 6.00 ± 0.67 μM and a Hill coefficient of 1.33 ± 0.18. BMS did not affect the steady-state activation of L-type Ca(2+) channels. However, for those in steady-state inactivation, BMS shifted the half-maximal potential (V(1/2)) by -11 mV, but the slope value (k) was not altered. Iberiotoxin, inhibitor of membrane BK(Ca) channels and paxilline, inhibitor of mitochondrial BK(Ca) channel did not affect the inhibitory effect of BMS on L-type Ca(2+) channels. Pretreatment with inhibitors of protein kinase A (PKA), protein kinase C (PKC), and protein kinase G (PKG) did not significantly alter the inhibitory effect of BMS on L-type Ca(2+) current. The presence of a selective β-adrenergic receptor agonist, isoproterenol did not affect the inhibitory effect of BMS on L-type Ca(2+) current. Based on these results, we concluded that the inhibition of L-type Ca(2+) channels by BMS is independent of the inhibition of BK(Ca) channels or intracellular signaling pathways.
It is important to take BMS-204352 (BMS) effects on L-type Ca(2+) channels into consideration when using BMS as a BK(Ca) channel activator or therapeutic target in ventricular myocytes.
我们研究了 BMS-204352（BMS），一种大电导钙激活钾（BK（Ca））通道激活剂，对 L 型钙（Ca2+）通道的影响。
在分离的大鼠心室肌细胞中进行电生理记录。采用全细胞构型。
BMS 以剂量依赖的方式抑制 Ca2+电流，Kd 为 6.00±0.67 μM，Hill 系数为 1.33±0.18。BMS 不影响 L 型 Ca2+通道的稳态激活。然而，对于那些处于稳态失活的通道，BMS 将半最大电位（V1/2）负移-11 mV，但斜率值（k）不变。Iberiotoxin，膜 BK（Ca）通道抑制剂和 Paxilline，线粒体 BK（Ca）通道抑制剂不影响 BMS 对 L 型 Ca2+通道的抑制作用。PKA、PKC 和 PKG 抑制剂预处理对 BMS 抑制 L 型 Ca2+电流的作用没有显著影响。选择性β肾上腺素能受体激动剂异丙肾上腺素的存在并不影响 BMS 对 L 型 Ca2+电流的抑制作用。基于这些结果，我们得出结论，BMS 对 L 型 Ca2+通道的抑制作用独立于 BK（Ca）通道或细胞内信号通路的抑制。
当将 BMS 作为心室肌细胞中 BK（Ca）通道激活剂或治疗靶点使用时，需要考虑 BMS 对 L 型 Ca2+通道的影响。
