Facilitation of Ca2+-activated K+ channels (IKCa1) by mibefradil in B lymphocytes

Pflügers Archiv : European journal of physiology
Hae Young YooSung Joon Kim

Abstract

K+ channels play critical roles in the proliferation and activation of lymphocytes. Mouse B cells express large-conductance background K+ channel (LK bg) 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 LK bg current with half inhibitory concentration (IC50), 1.9 and 2.3 microM, 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 microM), 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 microM mibefradil. The hyperpolarizing response was abolished by charybdotoxin, a selective bloc...Continue Reading

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Citations

Feb 9, 2016·Autoimmunity Reviews·Anantha Maharasi RamaKrishnan, Kavitha Sankaranarayanan
Dec 22, 2010·The Journal of Physiology·Ivana Y-T KuoCaryl E Hill
Jul 6, 2014·TheScientificWorldJournal·Wei WangXiaoxia Li
Oct 26, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Shinkyu ChoiSuk Hyo Suh
Dec 5, 2019·Channels·Gang FanMario Kassmann
Aug 14, 2019·Immunological Reviews·Trisha Mahtani, Bebhinn Treanor

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