The role of intracellular Mg^<2+> and its mechanism in the regulation of cardiac Ca channels

细胞内Mg^<2>在心脏Ca通道调节中的作用及其机制

• 批准号: 07670054
• 负责人: YAMAOKA Kaoru
• 金额: $ 1.22万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670054/
• 关键词: L-type Ca channel; frog; cardiac muscle; magnesium; calcium; GTP; phosphorylatioin; Caチャンネル; マグネシウムイオン; カルシウムイオン; グアノシンヌクレオタイド

This project revealed a great detail about action of intracellular Mg^<2+> on the L-type Ca channels in frog ventricular myocytes and indicated a physiological role of Mg^<2+> in the final step of the beta-adrenergic signal transduction pathway as follows.1.Decrease in the concentration of intracelluar Mg^<2+> ([Mg^<2+>]_i) down to 1 muM resulted in increase in L-type Ca current (I_<Ca>) up to 10 times of the control. This was not mediated through phosphorylation nor GTP-binding protein but possibly by direct biding of Mg^<2+> to the channel. I_<Ca>- [Mg^<2+>]_i relationship was obtained and this relationship indicated that 80-90% of channels are inactivated under phsyiological [Mg^<2+>]_i.2.Increase in the intracellular concentration of Ca^<2+> ([Ca^<2+>]_i) induce increase in I_<Ca>. This phenomenon is mediated through unblock of Mg^<2+> because Ca^<2+> competes for the site with Mg^<2+> and unbinds Mg^<2+>.3.Increase in I_<Ca> by reducing [Mg^<2+>]_i was inhibited in the presence of intracellular GTP.This phenomenon has been shown for the first time. The inhibition by GTP was not mediated through GTP-binding protein but by its direct binding to the channel competetively with Mg^<2+>.4.Phosphorylation of the L-type Ca channel altered the relationship between I_<Ca> and [Mg^<2+>]_i so that change in [Mg^<2+>]_i between 1muM and 1 mM did not induce change in I_<Ca> while I_<Ca> remained in the maximum value. This result provoked the idea that phosphorylation increases I_<Ca> by means of reducing the sensitivity of Ca channels to the blocking action of Mg^<2+> and, therefore, both channel phosphorylation and reduction of [Mg^<2+>]_i may share a common final step in modulation of the channel.

本研究揭示了胞内Mg^&lt;2+&gt;对蛙心室肌细胞L-型钙通道的作用，并指出Mg^&lt;2+&gt;在β-肾上腺素能信号转导通路的最后一步中的生理作用如下：1.胞内Mg^&lt;2+&gt;（[Mg^&lt;2+&gt;]_i）浓度降低至1 μ M时，L-型钙通道电流（I_i）增加<Ca>至对照的10倍。这既不是通过磷酸化也不是通过GTP结合蛋白介导的，而是可能通过Mg^&lt;2+&gt;与通道的直接结合。结果<Ca>表明，在生理[Mg ^&lt;2 +&gt;]_i作用下，80-90%的通道失活。2.细胞内Ca^&lt;2+&gt;浓度（[Ca^&lt;2+]_i）的增加引起I_i的增加<Ca>。这一现象是通过解除Mg^&lt;2+&gt;的阻断而介导的，因为Ca^&lt;2 +&gt;与Mg^&lt;2 +&gt;竞争位点，解除Mg ^<Ca>&lt;2+&gt;的结合. 4. L型钙通道的磷酸化改变了I_2与[Mg ^&lt;2+&gt;]_i之间的关系<Ca>，使[Mg ^&lt;2 +&gt;]_i在1 μ M和1 mM之间的变化不引起I_2的变化，<Ca>而I_2<Ca>保持在最大值。这一结果引发了这样的想法，即磷酸化<Ca>通过降低Ca通道对Mg^&lt;2+&gt;阻断作用的敏感性来增加I_i，因此，通道磷酸化和[Mg^&lt;2+&gt;]_i的减少可能在通道调节中共享共同的最后一步。

项目成果

Yamaoka,K.: "Regulation of Ca channel by interacellular Ca2+ and Mg2+ in frog ventricular cells." Pflugers Arch. 431. 305-317 (1996)

Yamaoka,K.：“青蛙心室细胞中细胞间 Ca2 和 Mg2 调节 Ca2+ 通道。”