Title: The inhibitory effect of Ca(2+)-activated K(+) channel activator, BMS on L-type Ca(2+) channels in rat ventricular myocytes.

Authors: Youn Kyoung Son, Seong Woo Choi, Won-Kyo Jung, Su-Hyun Jo, In Duk Jung, Yeong-Min Park, Il-Whan Choi, Jeong-Im Sin, Eun Bo Shim, Nari Kim, Jin Han, Won Sun Park

Journal, date & volume: Life Sci., 2011 Aug 29 , 89, 331-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21763323

Abstract
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.