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Life Sci. 2011 Aug 29;89(9-10):331-6. doi: 10.1016/j.lfs.2011.06.017. Epub 2011 Jul 7.

The inhibitory effect of Ca2+-activated K+ channel activator, BMS on L-type Ca2+ channels in rat ventricular myocytes.

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  • 1Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701, Republic of Korea.

Abstract

AIMS:

We investigated the effects of BMS-204352 (BMS), a big-conductance calcium-activated potassium (BK(Ca)) channel activator, on L-type Ca(2+) channels.

MAIN METHODS:

Electrophysiological recordings were performed in isolated rat ventricular myocytes. Whole-cell configuration was used.

KEY FINDINGS:

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.

SIGNIFICANCE:

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21763323
[PubMed - indexed for MEDLINE]
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