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- Title
Facilitation of Ca<sup>2+</sup>-activated K<sup>+</sup> channels (IKCa1) by mibefradil in B lymphocytes.
- Authors
Hae Young Yoo; Haifeng Zheng; Joo Hyun Nam; Yen Hoang Nguyen; Tong Mook Kang; Yung E. Earm; Sung Joon Kim
- Abstract
K+ channels play critical roles in the proliferation and activation of lymphocytes. Mouse B cells express large-conductance background K+ channel (LKbg) in addition to the voltage-gated K+ channel (Kv) and Ca2+-activated K+ channel current (IKCa1). Mibefradil, a blocker of T-type Ca2+ channels, has been reported to affect the proliferation of immune cells. In this study, we investigated the effects of mibefradil on the membrane potential and ion channels in murine B cell lines, WEHI-231 and Bal-17. In the whole-cell patch clamp experiments, mibefradil blocked Kv and LKbg current with half inhibitory concentration (IC50), 1.9 and 2.3 μM, respectively. Interestingly, IKCa1 current was increased by mibefradil. In the inside-out patch clamp study with cloned murine IKCa1 (mIKCa1) in HEK-293, mibefradil increased both Ca2+ sensitivity and maximum activity of mIKCa1. At high concentrations (>10 μM), mibefradil inhibited mIKCa1 in a voltage-dependent manner. Application of anti-IgM antibody to stimulate B cell receptors (BCR-ligation) induced transient hyperpolarization of Bal-17 and WEHI-231 cells, which became persistent with 1 μM mibefradil. The hyperpolarizing response was abolished by charybdotoxin, a selective blocker for SK4/IKCa1. In summary, our study firstly reports the ion channel-activating effects of mibefradil. The selective potent activation of IKCa1 suggests that mibefradil-derived drugs might be useful in the control of cell responses related with IKCa1.
- Subjects
LYMPHOCYTES; B cells; CELL proliferation; CELL lines; ION channels
- Publication
Pflügers Archiv: European Journal of Physiology, 2008, Vol 456, Issue 3, p549
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-007-0438-5