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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.4
- 수록면
- 322 - 329 (8page)
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Voltage-gated Ca2+ (CaV) channels are dynamically modu-lated by G protein-coupled receptors (GPCR). The M1 muscarinic receptor stimulation is known to enhance CaV2.3 channel gating through the activation of protein kinase C (PKC). Here, we found that M1 receptors also inhibit CaV2.3 currents when the channels are fully activated by PKC. In whole-cell configuration, the application of phorbol 12-myristate 13-acetate (PMA), a PKC activator, potentiated CaV2.3 currents by ~two-fold. After the PMA-induced potentiation, stimulation of M1 receptors decreased the CaV2.3 currents by 52 ? 8%. We examined whether the depletion of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is responsible for the muscarinic suppression of CaV2.3 currents by using two methods: the Danio rerio voltage-sensing phosphatase (Dr-VSP) system and the rapamycin-induced translocatable pseudojanin (PJ) system. First, dephosphorylation of PI(4,5)P2 to phosphatidylinositol 4-phosphate (PI(4)P) by Dr-VSP significantly suppressed CaV2.3 currents, by 53 ? 3%. Next, dephosphorylation of both PI(4)P and PI(4,5)P2 to PI by PJ translocation further decreased the current by up to 66 ? 3%. The results sug-gest that CaV2.3 currents are modulated by the M1 receptor in a dual mode?that is, potentiation through the activation of PKC and suppression by the depletion of membrane PI(4,5)P2. Our results also suggest that there is rapid turnover between PI(4)P and PI(4,5)P2 in the plasma membrane.
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참고문헌 (46)
참고문헌 신청
Balla, T / 2013 / Phosphoinositides : tiny lipids with giant impact on cell regulation / Physiol. Rev 93:1019~1137
Bannister, R. A. / 2004 / Differential modulation of CaV2. 3 Ca2+ channels by Gαq/11-coupled muscarinic receptors / Mol. Pharmacol 65:381~388
Bielas, S. L. / 2009 / Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies / Nat. Genet 41:1032~1036
Dickson, E. J. / 2014 / Golgi and plasma membrane pools of PI(4)P contribute to plasma membrane PI(4, 5)P2 and maintenance of KCNQ2/3 ion channel current / Proc. Natl. Acad. Sci. USA 111:2281~2290
Fang, H. / 2005 / Role of α1 2. 3 subunit Ⅰ-Ⅱ linker sites in the enhancement of CaV2. 3 current by phorbol 12-myristate 13-acetate and acetyl-β-methylcholine / J. Biol. Chem 208:23559~23565
Bannister, R. A. / 2004 / Differential modulation of CaV2. 3 Ca2+ channels by Gαq/11-coupled muscarinic receptors / Mol. Pharmacol 65:381~388
Bielas, S. L. / 2009 / Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies / Nat. Genet 41:1032~1036
Dickson, E. J. / 2014 / Golgi and plasma membrane pools of PI(4)P contribute to plasma membrane PI(4, 5)P2 and maintenance of KCNQ2/3 ion channel current / Proc. Natl. Acad. Sci. USA 111:2281~2290
Fang, H. / 2005 / Role of α1 2. 3 subunit Ⅰ-Ⅱ linker sites in the enhancement of CaV2. 3 current by phorbol 12-myristate 13-acetate and acetyl-β-methylcholine / J. Biol. Chem 208:23559~23565
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