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Choi SH, Lee BH, Hwang SH, et al. Molecular mechanisms of large-conductance ca (2+) -activated potassium channel activation by ginseng gintonin. Evid Based Complement Alternat Med. 2013;2013:323709doi: 10.1155/2013/323709.
Choi, S. H., Lee, B. H., Hwang, S. H., Kim, H. J., Lee, S. M., Kim, H. C., Rhim, H. W., & Nah, S. Y. (2013). Molecular mechanisms of large-conductance ca (2+) -activated potassium channel activation by ginseng gintonin. Evidence-based complementary and alternative medicine : eCAM, 2013323709. https://doi.org/10.1155/2013/323709
Choi, S H, et al. "Molecular mechanisms of large-conductance ca (2+) -activated potassium channel activation by ginseng gintonin." Evidence-based complementary and alternative medicine : eCAM vol. 2013 (2013): 323709. doi: https://doi.org/10.1155/2013/323709
Choi SH, Lee BH, Hwang SH, Kim HJ, Lee SM, Kim HC, Rhim HW, Nah SY. Molecular mechanisms of large-conductance ca (2+) -activated potassium channel activation by ginseng gintonin. Evid Based Complement Alternat Med. 2013;2013:323709. doi: 10.1155/2013/323709. Epub 2013 Apr 04. PMID: 23662129; PMCID: PMC3638619.
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Evid Based Complement Alternat Med. 2013;2013:323709. doi: 10.1155/2013/323709. Epub 2013 Apr 04.

Molecular mechanisms of large-conductance ca (2+) -activated potassium channel activation by ginseng gintonin.

Evidence-based complementary and alternative medicine : eCAM

S H Choi, B H Lee, S H Hwang, H J Kim, S M Lee, H C Kim, H W Rhim, S Y Nah

Affiliations

  1. Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea.

PMID: 23662129 PMCID: PMC3638619 DOI: 10.1155/2013/323709

Abstract

Gintonin is a unique lysophosphatidic acid (LPA) receptor ligand found in Panax ginseng. Gintonin induces transient [Ca(2+)]i through G protein-coupled LPA receptors. Large-conductance Ca(2+)-activated K(+) (BKCa) channels are expressed in blood vessels and neurons and play important roles in blood vessel relaxation and attenuation of neuronal excitability. BKCa channels are activated by transient [Ca(2+)]i and are regulated by various Ca(2+)-dependent kinases. We investigated the molecular mechanisms of BKCa channel activation by gintonin. BKCa channels are heterologously expressed in Xenopus oocytes. Gintonin treatment induced BKCa channel activation in oocytes expressing the BKCa channel α subunit in a concentration-dependent manner (EC50 = 0.71 ± 0.08 µg/mL). Gintonin-mediated BKCa channel activation was blocked by a PKC inhibitor, calphostin, and by the calmodulin inhibitor, calmidazolium. Site-directed mutations in BKCa channels targeting CaM kinase II or PKC phosphorylation sites but not PKA phosphorylation sites attenuated gintonin action. Mutations in the Ca(2+) bowl and the regulator of K(+) conductance (RCK) site also blocked gintonin action. These results indicate that gintonin-mediated BKCa channel activations are achieved through LPA1 receptor-phospholipase C-IP3-Ca(2+)-PKC-calmodulin-CaM kinase II pathways and calcium binding to the Ca(2+) bowl and RCK domain. Gintonin could be a novel contributor against blood vessel constriction and over-excitation of neurons.

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