INACTIVATION OF THE LOW-THRESHOLD TRANSIENT CALCIUM CURRENT IN RAT SENSORY NEURONS - EVIDENCE FOR A DUAL PROCESS
INACTIVATION OF THE LOW-THRESHOLD TRANSIENT CALCIUM CURRENT IN RAT SENSORY NEURONS - EVIDENCE FOR A DUAL PROCESS
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DOI：
10.1113/jphysiol.1986.sp016157
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发表时间：
1986-07-01
影响因子：
5.5
通讯作者：
FELTZ, A
中科院分区：
文献类型：
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作者：
BOSSU, JL;FELTZ, A
1. 在大鼠颅感觉神经元中，通过将膜电位从 -80 mV 去极化至超过 -50 mV 来引发瞬态 Ca 电流 (iCa,t)。本文描述了该电流的慢速和快速失活过程的特征。记录是在全细胞钳条件下从负载铯的细胞获得的。对于大多数实验，细胞在内部 pCa 为 8 时进行透析，并使用含有 5 mM-Ca 和 2 mM-Mg 的不含氯化胆碱和 K 的外部介质消除 Na 和 K 电流。 2. iCa,t 的衰减可以通过具有电压相关时间常数的单指数来近似拟合，该时间常数从-50 mV 时的约150 ms 减少到-20 mV 时的约25 ms。这表明失活过程是单一的，但对失活的开始和抵消的详细动力学分析揭示了双相过程。 3. 失活的开始表现出两个指数阶段。快相持续100-500毫秒，慢相持续几秒。每个阶段的相对幅度和时间常数随失活电位的变化而变化。 4.失活的恢复也是双相的，主要是快速或慢速成分，这取决于是否使用短（约数百毫秒）或长（约数十秒）失活脉冲。在 -80 mV 时，在 300 ms 失活脉冲后，响应在 200 ms 内恢复到至少最大值的 40%，并在 1 s 内完成恢复；长时间预除极（10-20 秒）后，恢复需要 4-5 秒。在大而短暂的去极化后观察到快速恢复最好，在小幅度的长时间失活预脉冲后观察到缓慢恢复最好。 5.通过实现失活曲线来确定慢速和快速失活的电压依赖性。在 -60 至 -20 mV 之间发生快速失活，而缓慢的过程发生在更超极化的电位，例如-75 至 -50 mV。 6. 在通道的先前激活过程中，Ca 的进入不会改变快速失活。当 Ba 取代 Ca 或内部 pCa 降低时，iCa,t 的进一步衰减不会改变。这些表明了独特的电压相关过程。讨论了 Ca 进入在缓慢失活中的可能作用。 7.将内部Ca浓度从5倍增加。 10-10 至 10-7 M 使两种类型的失活曲线向更超极化的电位有差异地移动。 8. 失活的两个组成部分可以被识别为 Ca 通道的两种不同的失活状态。
1. In rat cranial sensory neurones a transient Ca current (iCa,t) is elicited by depolarizing the membrane potential from -80 mV to beyond -50 mV. In this paper the characteristics of the slow and fast inactivation processes of this current are described. Recordings were obtained in whole-cell clamp conditions from Cs-loaded cells. For most experiments, cells were dialysed at an internal pCa of 8, and Na and K currents were eliminated using a choline chloride- and K-free external medium containing 5 mM-Ca and 2 mM-Mg. 2. The decay of iCa,t could be approximately fitted by a single exponential with a voltage-dependent time constant which decreased from about 150 ms at -50 mV to about 25 ms at -20 mV. This suggests a single process of inactivation but a detailed kinetic analysis of the onset and the offset of the inactivation revealed biphasic processes. 3. The onset of inactivation displays two exponential phases. The fast phase lasts for 100-500 ms, and the slow phase lasts for a few seconds. The relative amplitude and the time constants of each phase vary with the inactivating potential. 4. The recovery from inactivation is also biphasic, with either a fast or a slow component predominating, depending on whether a short- (some hundreds of milliseconds) or a long- (in the order of tens of seconds) inactivating pulse has been used. At -80 mV, after a 300 ms inactivating pulse, responses recover to at least 40% of maximum within 200 ms and recovery is complete within 1 s; after a long predepolarization (10-20 s), recovery takes 4-5 s. Fast recovery was observed best after large but brief depolarizations and slow recovery was observed best following long inactivating pre-pulses of small amplitude. 5. The voltage-dependence of slow and fast inactivation was determined by realizing inactivation curves. Fast inactivation developed between -60 and -20 mV while the slow process occurred at more hyperpolarized potentials, e.g. at -75 to -50 mV. 6. Fast inactivation was not altered by the entry of Ca during the previous activation of the channel. Further decay of iCa,t was not modified when Ba was substituted for Ca or the internal pCa was decreased. These are indications of a uniquely voltage-dependent process. A possible role of Ca entry in slow inactivation is discussed. 7. Increasing the internal Ca concentration from 5 .times. 10-10 to 10-7 M differentially shifted both types of inactivation curves towards more hyperpolarized potentials. 8. The two components of inactivation can be identified as two distinct inactivated states of the Ca channel.