The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Activation of Lysophosphatidic Acid Receptor Is Coupled to Enhancement of $Ca^{2+}$ -Activated Potassium Channel Currents

  • Choi, Sun-Hye (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Lee, Byung-Hwan (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Hyeon-Joong (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Hwang, Sung-Hee (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Lee, Sang-Mok (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Nah, Seung-Yeol (Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University)
  • Received : 2013.04.01
  • Accepted : 2013.05.22
  • Published : 2013.06.30
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Abstract

The calcium-activated $K^+$ ($BK_{Ca}$) channel is one of the potassium-selective ion channels that are present in the nervous and vascular systems. $Ca^{2+}$ is the main regulator of $BK_{Ca}$ channel activation. The $BK_{Ca}$ channel contains two high affinity $Ca^{2+}$ binding sites, namely, regulators of $K^+$ conductance, RCK1 and the $Ca^{2+}$ 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 $Ca^{2+}$ levels through diverse G proteins such as $G{\alpha}_{q/11}$, $G{\alpha}_i$, $G{\alpha}_{12/13}$, and $G{\alpha}s$ and the related signal transduction pathway. In the present study, we examined LPA effects on $BK_{Ca}$ 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 $BK_{Ca}$ channel activation was also attenuated by the PLC inhibitor U-73122, $IP_3$ inhibitor 2-APB, $Ca^{2+}$ chelator BAPTA, or PKC inhibitor calphostin. In addition, mutations in RCK1 and RCK2 also attenuated LPA-mediated $BK_{Ca}$ channel activation. The present study indicates that LPA-mediated activation of the $BK_{Ca}$ channel is achieved through the PLC, $IP_3$, $Ca^{2+}$, and PKC pathway and that LPA-mediated activation of the $BK_{Ca}$ channel could be one of the biological effects of LPA in the nervous and vascular systems.

Keywords

References

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