Fast inactivation of Nav current in rat adrenal chromaffin cells involves two independent inactivation pathways.
Fast inactivation of Nav current in rat adrenal chromaffin cells involves two independent inactivation pathways.
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DOI：
10.1085/jgp.202012784
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发表时间：
2021-04-05
期刊：
影响因子：
--
通讯作者：
Lingle CJ
中科院分区：
文献类型：
--
作者：
Martinez-Espinosa PL;Neely A;Ding J;Lingle CJ
马丁内斯-埃斯皮诺萨等人。结果表明，大鼠肾上腺嗜铬细胞电压依赖性钠离子通道的快速和缓慢恢复依赖于两条独立的失活途径。这些途径之间的竞争调节着NAV通道可用性的变化。肾上腺嗜铬细胞(CCS)的电压依赖性钠(Nav)电流迅速失活，对河豚毒素(TTX)敏感。CC Nav电流的分数可用性与动作电位(AP)频率的调节和慢波爆发放电的发生有关。在这里，通过记录大鼠CCS的NAV电流，主要是在肾上腺髓质切片上，我们描述了CC Nav失活的独特的失活特性，这有助于确定CCS中的AP放电率。CC Nav电流的主要特征是从失活中恢复，即使在短暂的失活步骤(5ms)之后，也显示出两个幅度相似的指数分量。不同的成对脉冲方案表明，进入快速和较慢的恢复过程是由基本上独立的竞争失活途径引起的，每一种失活途径在去极化电位下都有相似的起始时间。在从−120到−80 mV的电压范围内，较快的恢复速度在∼3到30 ms之间变化，而较慢的恢复速度在∼50到400 ms之间变化。在强去极化条件下(−10 mV以上)，相对进入慢、快恢复通道的情况相似，且与电压无关。短去极化的序列有利于从快速恢复路径恢复，并导致缓慢恢复分数的累积增加。双途径快速失活，通过促进缓慢恢复途径中的使用依赖积累，动态调节NAV的可用性。与这一发现一致的是，1-10赫兹频率的重复AP钳制波形会使NAV的可用性降低80%-90%，具体取决于保持电位。这些结果表明，存在两种不同的快速失活途径，一种是导致常规快速恢复的途径，另一种是导致较慢恢复的途径，这两条途径共同适合于调节NAV可用性的使用依赖变化。
Martinez-Espinosa et al. show that fast and slow recovery of voltage-dependent Na+ (Nav) channels in rat adrenal chromaffin cells depends on two independent inactivation pathways. Competition between these pathways regulates changes in Nav channel availability. Voltage-dependent sodium (Nav) current in adrenal chromaffin cells (CCs) is rapidly inactivating and tetrodotoxin (TTX)–sensitive. The fractional availability of CC Nav current has been implicated in regulation of action potential (AP) frequency and the occurrence of slow-wave burst firing. Here, through recordings of Nav current in rat CCs, primarily in adrenal medullary slices, we describe unique inactivation properties of CC Nav inactivation that help define AP firing rates in CCs. The key feature of CC Nav current is that recovery from inactivation, even following brief (5 ms) inactivation steps, exhibits two exponential components of similar amplitude. Various paired pulse protocols show that entry into the fast and slower recovery processes result from largely independent competing inactivation pathways, each of which occurs with similar onset times at depolarizing potentials. Over voltages from −120 to −80 mV, faster recovery varies from ∼3 to 30 ms, while slower recovery varies from ∼50 to 400 ms. With strong depolarization (above −10 mV), the relative entry into slow or fast recovery pathways is similar and independent of voltage. Trains of short depolarizations favor recovery from fast recovery pathways and result in cumulative increases in the slow recovery fraction. Dual-pathway fast inactivation, by promoting use-dependent accumulation in slow recovery pathways, dynamically regulates Nav availability. Consistent with this finding, repetitive AP clamp waveforms at 1–10 Hz frequencies reduce Nav availability 80–90%, depending on holding potential. These results indicate that there are two distinct pathways of fast inactivation, one leading to conventional fast recovery and the other to slower recovery, which together are well-suited to mediate use-dependent changes in Nav availability.
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DOI：
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发表时间：
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期刊：
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