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

肌肉和神经元中l型钙通道的活动受到细胞内钙浓度的反馈控制（[Ca]i），其中包括钙依赖性失活和增强。然而，人们对这两种相反功能之间的相互关系以及所需的[Ca]水平知之甚少。通过fura2对[Ca]i的同时光学监测，我们在单通道水平上研究了[Ca]i的强直变化如何调节心脏l型Ca通道。当钾去极化状态下肌细胞的胞浆钙浓度通过钙离子浓度的变化而改变时，当[Ca]i超过静息水平的2倍时，钙离子通道的活性可逆地增强，直到它达到低于收缩阈值的“失活”水平。在这些观察中，单一电流振幅是恒定的。钙依赖性增强过程中通道打开的可能性增加与1有关。增加了可用扫描次数，2。开放扫瞄时Po值增加；增加了model2行为的外观。我们还发现，钙依赖性增强具有短期“记忆”，可以抵抗短暂的钙诱导失活。本研究首次对钙通道活性的钙依赖性进行了直接定量分析。

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.