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

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。

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.