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KMID : 0811720130170030223
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Korean Journal of Physiology & Pharmacology
2013 Volume.17 No. 3 p.223 ~ p.228
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Activation of Lysophosphatidic Acid Receptor Is Coupled to Enhancement of Ca2＋-Activated Potassium Channel Currents
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Choi Sun-Hye
Lee Byung-Hwan
Kim Hyeon-Joong
Hwang Sung-Hee
Lee Sang-Mok
Nah Seung-Yeol
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Abstract
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The calcium-activated K＋ (BKCa) channel is one of the potassium-selective ion channels that are present in the nervous and vascular systems. Ca2＋ is the main regulator of BKCa channel activation. The BKCa channel contains two high affinity Ca2＋ binding sites, namely, regulators of K＋ conductance, RCK1 and the Ca2＋ bowl. Lysophosphatidic acid (LPA, 1-radyl-2-hydroxy-sn-glycero-3-phosphate) is one of the neurolipids. LPA affects diverse cellular functions on many cell types through G protein- coupled LPA receptor subtypes. The activation of LPA receptors induces transient elevation of intracellular Ca2＋ levels through diverse G proteins such as G?q/11, G?i, G?12/13, and G?s and the related signal transduction pathway. In the present study, we examined LPA effects on BKCa channel activity expressed in Xenopus oocytes, which are known to endogenously express the LPA receptor. Treatment with LPA induced a large outward current in a reversible and concentration-dependent manner. However, repeated treatment with LPA induced a rapid desensitization, and the LPA receptor antagonist Ki16425 blocked LPA action. LPA-mediated BKCa channel activation was also attenuated by the PLC inhibitor U-73122, IP3 inhibitor 2-APB, Ca2＋ chelator BAPTA, or PKC inhibitor calphostin. In addition, mutations in RCK1 and RCK2 also attenuated LPA-mediated BKCa channel activation. The present study indicates that LPA-mediated activation of the BKCa channel is achieved through the PLC, IP3, Ca2＋, and PKC pathway and that LPA-mediated activation of the BKCa channel could be one of the biological effects of LPA in the nervous and vascular systems.
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KEYWORD
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BKCa channels, Ca2＋ signal pathways, LPA, LPA receptor, Xenopus oocytes
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