CA CURRENT FACILITATION DURING POSTREST RECOVERY DEPENDS ON CA ENTRY
CA CURRENT FACILITATION DURING POSTREST RECOVERY DEPENDS ON CA ENTRY
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DOI：
10.1152/ajpheart.1990.259.3.h951
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发表时间：
1990-09-01
影响因子：
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通讯作者：
BERS, DM
中科院分区：
文献类型：
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作者：
HRYSHKO, LV;BERS, DM
在电压钳位抑制Na和K电流的兔心室肌细胞中，观察了静息期后全细胞Ca电流（伊卡）的恢复。为了评估不依赖于肌浆网（SR）Ca释放的影响的伊卡的静息依赖性变化，细胞内Ca（[Ca]i）瞬变通常由乙二醇-双（β-葡萄糖）缓冲。氨基乙基醚）-N，N，N“N”-四乙酸（10 mM）。当电压钳脉冲恢复（0.5 Hz）后，休息一段时间，需要几个脉冲重新达到稳态峰值伊卡水平。从-40和-50 mV之间的去极化保持电位，第一个脉冲的峰值伊卡很大，并逐渐衰减到稳态水平（负伊卡阶梯）。这种增强休息后的伊卡介导的增加恢复失活的Ca通道在休息期间。相反，在更负的保持电位（-70至-90 mV）下，初始静息后伊卡相对较小（静息抑制），然后观察到后续脉冲的伊卡易化（正伊卡阶梯）。这种伊卡便利化是由伊卡失活率的逐步降低介导的。初始静息后伊卡的抑制需要10-15 s的静息才能完全发展，并且在较长的静息间隔（30-300 s）内变得相对恒定。静息后伊卡降低（即，通过用Ba或Sr替换细胞外Ca（[Ca]o）来消除随后的伊卡促进。因此，伊卡促进依赖于Ca进入。增加[Ca]o增加静息后伊卡易化，而减少[Ca]o则有相反的作用。当通过改变阶跃电位改变伊卡时，最大的伊卡易化发生在伊卡最大时。因此，可以通过Ca进入量对ICa促进进行分级。由于Ryanodine不改变伊卡的易化作用，因此这种反应不太可能是由于SR Ca释放所致。然而，通过在移液管中使用1，2-双（2-氨基苯氧基）乙烷-N，N，N“，N”-四乙酸来增加[Ca]i缓冲消除了伊卡阶梯。我们的研究结果表明，钙进入可以促进随后的伊卡，大概是通过附近的肌膜发生的行动。[Ca]i的这些局部变化导致伊卡失活速率的进行性减慢。
Whole cell Ca current (ICa) recovery after periods of rest was examined in voltage-clamped rabbit ventricular myocytes with Na and K currents suppressed. To evaluate rest-dependent changes in ICa independent of the effects of sarcoplasmic reticular (SR) Ca release, the intracellular Ca ([Ca]i) transients were usually buffered by ethylene glycol-bis(.beta.-aminoethyl ether)-N,N,N''N''-tetraacetic acid (10 mM) in the patch pipette. When voltage-clamp pulses were resumed (at 0.5 Hz) after a period of rest, several pulses were required to reattain steady-state peak ICa levels. From depolarized holding potentials between -40 and -50 mV, peak ICa of the first pulse was large and gradually decayed to steady-state levels (negative ICa staircase). This potentiation of postrest ICa was mediated by increased recovery from inactivation of Ca channels during the rest period. In contrast, with more negative holding potentials (-70 to -90 mV), the initial postrest ICa was relatively small (rest depression) and facilitation of ICa was then observed for subsequent pulses (positive ICa staircase). This ICa facilitation was mediated by a progressive decrease in the ICa inactivation rate. Depression of the initial postrest ICa required 10-15 s of rest to fully develop and became relatively constant for longer rest intervals (30-300 s). Postrest ICa depression (i.e., subsequent ICa facilitation) was abolished by replacement of extracellular Ca ([Ca]o) with either Ba or Sr. Thus ICa facilitation depends on Ca entry. Increasing [Ca]o increased postrest ICa facilitation and reducing [Ca]o had an opposite effect. When ICa was altered by changing step potential maximal ICa facilitation occurred when ICa was maximal. Thus ICa facilitation can be graded by the amount of Ca entry. As ICa facilitation was not altered by ryanodine, this response is not likely to be due to SR Ca release. However, increasing [Ca]i buffering by using 1,2-bis(2-aminophenoxy)ethane-N,N,N'',N''-tetraacetic acid in the pipette abolished the ICa staircase. Our results indicate that Ca entry can facilitate subsequent ICa, presumably through actions occurring near the sarcolemma. These local changes in [Ca]i lead to a progressive slowing in the rate of ICa inactivation.