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A selective T-type Ca2+ channel blocker R(−) efonidipine

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Abstract

Recently, novel compound R(−) efonidipine was reported to selectively block low-voltage-activated (LVA or T-type) Ca2+ channels in peripheral organs. We examined how R(−) efonidipine acts on T-type and high-voltage-activated (HVA) Ca2+ channels in mammalian central nervous system (CNS) neurons. Furthermore, we compared the effects of R(−) efonidipine with those of flunarizine and mibefradil on both T-type and HVA Ca2+ channels in rat hippocampal CA1 neurons by using the nystatin perforated-patch clamp technique. Flunarizine and mibefradil nonselectively inhibited both T-type and HVA Ca2+ channels, though the dose-dependent blocking potency of flunarizine on T-type Ca2+ channels was slightly stronger than that of mibefradil. In contrast, R(−) efonidipine inhibited only T-type Ca2+ channels and did not show any effect on HVA Ca2+ channels. The inhibitory actions of R(−) efonidipine or flunarizine were similar on both Ba2+ and Ca2+ current components passing through T-type Ca2+ channels. In addition, flunarizine but not R(−) efonidipine inhibited voltage-dependent Na+ channels and Ca2+-activated K+ channels. Thus, it appears that R(−) efonidipine is a selective blocker for T-type Ca2+ channels. It could be used as a pharmacological tool in future studies on T-type Ca2+ channels.

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Acknowledgments

The authors thank Dr. Andrew Moorhouse and Dr. Y. Ito for their valuable comments and advice. This work is supported by a grant to N. Akaike from the Project for Promoting Industry-Academic Collaborative Research and the Tokyo Biochemical Research Foundation (TBRF).

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Authors and Affiliations

  1. Research Division for Life Sciences, Kumamoto Health Science University, Kumamoto, 861-5598, Japan

    Min-Chul Shin, Chang-Ju Kim, Byung-Il Min, Sachie Ogawa & Norio Akaike

  2. Department of Physiology, College of Medicine, Kyung Hee University, #1 Hoigi-Dong, Dongdaemoon-Gu, Seoul, South Korea

    Min-Chul Shin, Chang-Ju Kim & Byung-Il Min

  3. Department of Physiology, Kurume University School of Medicine, Kurume, 830-0011, Japan

    Sachie Ogawa & Eiichiro Tanaka

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  1. Min-Chul Shin
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Correspondence to Norio Akaike.

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Supplementary Figure

Comparison of T-type Ca2+-channel I–V relationships with Ca2+ and Ba2+, as indicated. Holding voltage is −90 mV. The current traces were obtained from the same cell; 2.5 mM Ca2+ and 5 mM Ba2+ gave a difference of about 5 ∼ 10 mV on the voltage at which the peak current was obtained. (DOC 42 kb)

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Shin, MC., Kim, CJ., Min, BI. et al. A selective T-type Ca2+ channel blocker R(−) efonidipine. Naunyn-Schmied Arch Pharmacol 377, 411–421 (2008). https://doi.org/10.1007/s00210-007-0239-6

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