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

  • Life Sci. 2011 Aug 29;89(9-10):331-6. doi: 10.1016/j.lfs.2011.06.017.
Youn Kyoung Son  1 ,  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
Affiliations
  • 1. Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701, Republic of Korea.
PMID: 21763323 DOI: 10.1016/j.lfs.2011.06.017
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.

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