Characterization of acid-sensitive ion channels in freshly isolated rat brain neurons
Characterization of acid-sensitive ion channels in freshly isolated rat brain neurons
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DOI：
10.1016/s0306-4522(01)00582-6
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发表时间：
2002-01-01
期刊：
影响因子：
3.3
通讯作者：
Magazanik, LG
中科院分区：
文献类型：
--
作者：
Bolshakov, KV;Essin, KV;Magazanik, LG
在从大鼠脑新鲜分离的不同神经元（舌下神经运动神经元、小脑浦肯野细胞、纹状体巨大胆碱能中间神经元）中记录到细胞外pH从7.4快速变化至小于或等于6.8所诱导的瞬时质子激活电流。海马CA 1锥体神经元的反应较弱（100-300 pA），而其它类型的神经元的反应较弱（1-3 nA）。神经元对快速酸化的敏感性从舌下神经运动神经元的pH（50）6.4到海马中间神经元的4.9不等。质子激活电流被阿米洛利阻断（IC_（50）从3.6到9.5 μ M变化）。该电流的反射电位接近于E-Na，表明电流由钠离子携带。结果表明，所研究的神经元的质子激活电流是由酸敏感离子通道介导的。强酸化（pH < 4）在所有神经元类型中诱导双相反应：瞬时电流之后是明显的持续电流。持续电流不被阿米洛利阻断，对钠和铯离子的选择性较低。从pH 7.4到6.5的缓慢酸化没有诱导可检测的全细胞电流。在pH 6.5时，大多数通道被脱敏，并且对从该初始水平的最后pH变化的响应降低至少10倍，这表明，慢性酸化，这是众所周知的伴随着一些病理状态，而不是激活酸敏感离子通道和抑制其功能，而不是脱敏。敏感的离子通道由这些通道介导的电流的大幅度和瞬态特性表明，它们可能有助于快速的神经元信号传导过程。(C)2002年IBRO。由Elsevier Science Ltd出版，保留所有权利。
Transient proton-activated currents induced by rapid shifts of the extracellular pH from 7.4 to less than or equal to6.8 were recorded in different neurons freshly isolated from rat brain (hypoglossal motoneurons, cerebellar Purkinje cells, striatal giant cholinergic interneurons. hippocampal interneurons, CAl pyramidal neurons and cortical pyramidal neurons) using whole-cell patch clamp technique, Responses of hippocampal CAl pyramidal neurons were weak (100-300 pA) in contrast to other types of neurons (1-3 nA). Sensitivity of neurons to rapid acidification varied from pH(50) 6.4 in hypoglossal motoneurons to 4.9 in hippocampal interneurons. Proton-activated currents were blocked by amiloride (IC50 varied From 3.6 to 9.5 muM). Reversal potential of the currents was close to E-Na, indicating that the currents are carried by sodium ions. The data obtained suggest that the proton-activated Currents in the neurons studied are mediated by acid-sensitive ion channels. Strong acidification (pH < 4) induced biphasic responses in all neuron types: the transient current was followed by a pronounced sustained one. Sustained current was not blocked by amiloride and exhibited low selectivity for sodium and cesium ions. Slow acidification from pH 7,4 to 6.5 did not induce detectable whole-cell currents. At pH 6.5, most of the channels are desensitized and responses to last pH shifts from this initial level are decreased at least 10 times, This suggests that slow acidification which is well known to accompany some pathological states should rather desensitize than activate acid-sensitive ion channels and depress their function.Our results provide evidence for a widespread and neuron-specific distribution of acid-sensitive ion channels in the brain. The large amplitudes and transient character of currents mediated by these channels suggest that they could contribute to fast neuronal signaling processes. (C) 2002 IBRO. Published by Elsevier Science Ltd, All rights reserved.