Dual modulation of Ca channels by intracellular Ca^<2+> concentration

细胞内 Ca^2 浓度对 Ca 通道的双重调节

• 批准号: 03670443
• 负责人: HIRANO Yuji
• 金额: $ 1.28万
• 依托单位: Tokyo Medical and Dental University, Medical Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670443/
• 关键词: Ca channel; Intracellular Ca^<2+>; Fura 2; Patch clamp; Fura 2; カルシウム電流; 細胞内カルシウム濃度; fura2; 単離心筋細胞

Activities of L-type Ca channels in muscles and neurons are under feedback controls by intracellular Ca concentrations ([Ca]i), which include both Ca-dependent inactivation and potentiation. Little is known,however, about interrelationships between these two opposite functions and the levels of [Ca]i required. With simultaneous optical monitoring of [Ca]i using fura2, we investigated at the single-channel level how tonic changes in [Ca]i modulate cardiac L-type Ca channels. When cytosolic Ca concentrations of myocytes under K-depolarization is altered through changes in bath Ca concentration, activity of Ca channels is reversibly potentiated as [Ca]i exceeds 2 times the resting level, until it reaches the "inactivation" level shortly below the threshold for contraction. Unitary current amplitudes were constant during these observations. Increased probability for channel opening during Ca-dependent potentiation was associated with 1. increased number of available sweeps, 2. increased Po during open sweeps, and 3. increased appearance of "mode2" behavior. We also found that Ca-dependent potentiation was equipped with short term "memory" which is resistant to transient Ca-induced inactivation. The present study provide analysis of Ca-dependence of Ca channel activity for the first time in direct and quantitative way.

肌肉和神经元中L型钙通道的活动受细胞内钙浓度（[Ca]i）的反馈控制，包括钙依赖性失活和增强。然而，很少有人知道这两个相反的功能之间的相互关系和水平的[Ca]i所需的。通过使用fura 2同时光学监测[Ca]i，我们在单通道水平上研究了[Ca]i的紧张性变化如何调节心脏L型Ca通道。当K-去极化下的肌细胞的胞质Ca浓度通过浴Ca浓度的变化而改变时，Ca通道的活性可逆地增强，因为[Ca]i超过静息水平的2倍，直到其达到略低于收缩阈值的“失活”水平。在这些观察期间，单一电流振幅是恒定的。在钙依赖性增强过程中通道开放的可能性增加与1。增加可用扫描次数，2.在开放扫描期间增加Po，以及3.增加“模式2”行为的出现。我们还发现，钙依赖性增强配备了短期的“记忆”，这是抵抗瞬时钙诱导的失活。本研究首次以直接、定量的方法分析了钙通道活性的钙依赖性。

项目成果

Hirano,Y.& Abe,S.: "Arachidonic acid induced increase in intracellular free calcium in quineaーpig hepatocytes" Jpn.J.Physiol.41. 327-332 (1991)

Hirano, Y. & Abe, S.：“花生四烯酸诱导奎尼尔猪肝细胞内游离钙的增加”Jpn.J.Physiol.41 (1991)。

HIRANO Y & M.HIRAOKA: "Dual modulation of L-type Ca current by intracellular calcium:single channel recording from fura2 loaded guinea-pig ventricular myocytes." J.Physiol. (1993)

平野Y

Hirano,Y.& Abe,S.: "External ATPーinduced changes in [Ca^<2+>]i and membrane currents in mammalian atrial myocytes." Am.J.Physiol.29. C673-C680 (1991)

Hirano, Y. & Abe, S.：“哺乳动物心房肌细胞中 [Ca^2+]i 和膜电流的外部 ATP 诱导变化。Am.J.Physiol.29 (1991)”

平野 祐司,平岡 昌和: "不整脈とカルシウム" Clinical. (1993)

Yuji Hirano、Masakazu Hiraoka：“心律失常与钙”临床 (1993)。