The role of L-type Ca2+ current and Na+ current-stimulated Na/Ca exchange in triggering SR calcium release in guinea-pig cardiac ventricular myocytes
The role of L-type Ca2+ current and Na+ current-stimulated Na/Ca exchange in triggering SR calcium release in guinea-pig cardiac ventricular myocytes
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DOI：
10.1016/s0008-6363(97)00117-x
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发表时间：
1997-08-01
影响因子：
10.8
通讯作者：
Cannell, MB
中科院分区：
文献类型：
--
作者：
Evans, AM;Cannell, MB
目的：本研究探讨了钠电流（I-Na）刺激的反向Na/Ca交换和L型钙电流（I-Ca）触发豚鼠心室肌细胞钙诱导的钙释放（CICR）的相对能力。方法：使用Indo-1从酶促解离的豚鼠心室肌细胞记录胞浆Ca 2+瞬变。用全细胞膜片钳技术同时记录宏观膜电流。结果：在室温（22-25 ℃）下，Ca 2+瞬变与I-Na、I-Ca或I-Na + I-Ca联合激活有关。然而，在用维拉帕米（10 μ M）阻断I-Ca后，单独激活I-Na在-40或+5mV时均不能诱发Ca ~（2+）瞬变。用5和8 mM细胞内钠，以及当浴溶液的温度升高到35 ℃并将cAMP（10 μ M）加入到移液管溶液中时，获得了类似的结果。结论：从考虑的相对幅度的Ca 2+内流通过Ic，Na/Ca交换和热力学的考虑，我们认为，I-Ca是“触发”钙的CICR（和心脏收缩）在正常条件下的主要来源。虽然Na/Ca交换器是无法触发CICR在这些实验的条件下，我们认为，它可能会变得更加重要，当胞质Ca 2+升高，这也将导致降低的幅度I-Ca的条件。(C)1997年Elsevier Science B.V.
Objective: This study examines the relative ability of sodium current (I-Na)-stimulated reverse mode Na/Ca exchange and the L-type calcium current (I-Ca) to trigger calcium-induced calcium release (CICR) in guinea-pig ventricular myocytes. Methods: Cytosolic Ca2+ transients were recorded from enzymatically dissociated guinea-pig ventricular mycocytes using Indo-1. Macroscopic membrane currents were simultaneously recorded using the whole-cell patch-clamp technique. Results: At room temperature (22-25 degrees C) Ca2+ transients were associated with the activation of I-Na, I-Ca or I-Na plus I-Ca in combination. However, after I-Ca was blocked by verapamil (10 mu M), no Ca2+ transient could be evoked by the activation of I-Na alone at either -40 or +5 mV. Similar results were obtained with 5 and 8 mM intracellular sodium, and when the temperature of the bathing solution was raised to 35 degrees C and cAMP (10 mu M) added to the pipette solution. Conclusions: From consideration of the relative magnitudes of the Ca2+ influx via Ic, and Na/Ca exchange and thermodynamic considerations, we suggest that I-Ca is the major source of 'trigger' calcium for CICR (and cardiac contraction) under normal conditions. Although the Na/Ca exchanger was incapable of triggering CICR under the conditions of these experiments, we suggest that it may become more important when cytosolic Ca2+ is elevated, a condition which will also lead to decrease the amplitude of I-Ca. (C) 1997 Elsevier Science B.V.