Molecular mechanisms of inactivation process of L-type Ca2+ channel

L型Ca2通道失活过程的分子机制

• 批准号: 13670088
• 负责人: KAIBARA Muneshige
• 金额: $ 2.24万
• 依托单位: Nagasaki University Graduate School of Biomedical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670088/
• 关键词: L-type; calcium channel; CACNA1C; inactivation; phosphorylation; cAMP; protein kinase; patch clamp; Cavl2; Cav1.2

Calcium channel currents activate with membrane depolarization and inactivate overtime. The inactivating property has an important role in regulating intracellular Ca2+ concentration. Inactivation of the currents is modulated by at least tree factors : 1)membrane potential, 2) Ca2+, and 3) phosphorylation.In this study, we investigated molecular mechanisms of the inactivation process related to phosphorylation using expression system. We cloned CACNA1C from guinea pig heart. And we investigated the role of phosphorylation sites in CACNA1C with mutagenesis study using whole-cell patch clamp study.Our data indicate that 1) multiple phosphorylation sites in CACNA1are involved in the regulation of the channel activity, 2)other subunit regulates roles of each phosphorylation site in CACNA1C.We have cloned CACNA1C(AB092629) and KCNJ12 (AB074970).

钙通道电流随着时间的推移而激活，伴随着膜的去极化和去极化。失活特性在调节细胞内Ca ~（2+）浓度方面具有重要作用。该电流的失活至少受三个因素的调控：1）膜电位，2）Ca ~（2+），3）磷酸化。我们从豚鼠心脏中克隆了CACNA 1C。结果表明：1）CACNA 1C中的多个磷酸化位点参与了通道活性的调控; 2）其他亚基调控CACNA 1C中各个磷酸化位点的功能。

项目成果

Yoshida A: "5-Hydroxytryptamine receptors, especially the 5-HT4 receptor, in guinea pig urinary bladder"Jpn.J.Pharmacol. 89・4. 349-355 (2002)

吉田A：“豚鼠膀胱中的5-羟色胺受体，特别是5-HT4受体”Jpn.J.Pharmacol.89·4(2002)。

Yoshida A: "5-Hydroxytryptamine receptors, especially the 5-HT4 receptor, in guinea pig urinary bladder"Jpn.J.Pharmacol.. 89. 349-355 (2002)

吉田 A：“豚鼠膀胱中的 5-羟色胺受体，特别是 5-HT4 受体”Jpn.J.Pharmacol.. 89. 349-355 (2002)

Shiga Y: "The inhibitory effects of tramadol on muscarinic receptor-induced responses in Xenopus oocytes expressing cloned M(3) receptors"Anesth.Analg.. 95. 1269-1273 (2002)

Shiga Y：“曲马多对表达克隆 M(3) 受体的爪蟾卵母细胞中毒蕈碱受体诱导的反应的抑制作用”Anesth.Analg.. 95. 1269-1273 (2002)

Matsuo, K.: "Involvement of cholinergic neurons in orexin-induced contraction of guinea pig ileum."Eur.J.Pharmacol.. 452・1. 105-109 (2002)

Matsuo, K.：“胆碱能神经元参与食欲素诱导的豚鼠回肠收缩”。Eur.J.Pharmacol.. 452・1 (2002)。

Kaibara, M.: "Identification of human Kir2.2 (KCNJ12) gene encoding functional inward rectifier potassium channel in both mammalian cells and Xenopus oocytes."FEBS Lett.. 531. 250-254 (2002)

Kaibara, M.：“哺乳动物细胞和非洲爪蟾卵母细胞中编码功能性内向整流钾通道的人类 Kir2.2 (KCNJ12) 基因的鉴定。”FEBS Lett.. 531. 250-254 (2002)