Role of the hyperpolarization-activated cation current (Ih) in pacemaker activity in area postrema neurons of rat brain slices
Role of the hyperpolarization-activated cation current (Ih) in pacemaker activity in area postrema neurons of rat brain slices
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DOI：
10.1113/jphysiol.2003.047191
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发表时间：
2003-10-01
影响因子：
5.5
通讯作者：
Matsuo, R
中科院分区：
文献类型：
--
作者：
Funahashi, M;Mitoh, Y;Matsuo, R
为了阐明超极化激活的阳离子电流（I-h）作为最后区神经元起搏电流的功能特性，在大鼠脑切片中视觉识别的细胞中进行全细胞记录。在大约62%的测试最后区神经元中识别出I-h的激活。在电流钳模式下，显示I-h的细胞对超极化电流注入表现出去极化的“下垂”。I-h的反转电位为-36 mV，这取决于Na+和K+离子的外部浓度。细胞外Cs ~+离子（2 mm）和选择性I-h通道拮抗剂ZD 7288（100 am）阻断I-h并诱导膜电位超极化，提示I-h在静息电位附近持续激活，并在更去极化水平对膜电位维持有贡献。相反，细胞外Ba 2+离子引起的膜电位去极化，这表明内向整流K+电流的封锁。ZD 7288通过延长两个尖峰之间的缓慢去极化降低自发放电率，对后超极化或动作电位波形的振幅影响极小。I-h稳定了动作电位的反弹潜伏期。I-h被外部8-溴腺苷3 '，5'环一磷酸（Imm）或毛喉素（50-100 μ m）弱激活，表明最后区细胞中的I-h通道亚型可被细胞内cAMP调节。我们的研究结果表明，I-h有助于阈下膜和放电特性的大鼠最后区。神经元，并可调节其静息膜电位和放电模式。
To clarify the functional properties of the hyperpolarization-activated cation current (I-h) as a pacemaker current in area postrema neurons, whole-cell recordings were made in visually identified cells in rat brain slices. The activation of I-h was identified in approximately 62% of area postrema neurons tested. The cells displaying I-h showed a depolarizing 'sag' in responses to hyperpolarizing current injection in current-clamp mode. The reversal potential for the I-h was -36 mV, and this was shown to depend on the external concentration of Na+ and K+ ions. Extracellular Cs+ ions (2 mm) and ZD7288 (100 am), a potent selective I-h channel antagonist, blocked I-h and induced a membrane potential hyperpolarization, suggesting the sustained activation of I-h near the resting potential and a contribution from I-h to membrane potential maintenance at more depolarized levels. In contrast, extracellular Ba2+ ions caused a depolarization of the membrane potential, suggesting the blockade of inward rectifier K+ currents. ZD7288 decreased the spontaneous discharge rate by prolonging the slow depolarization between two spikes, with minimal effect on the amplitude of the after-hyperpolarization or action potential waveforms. I-h stabilized the latency of rebound action potentials. I-h was weakly activated by external 8-bromoadenosine 3',5' cyclic monophosphate (I mm) or forskolin (50-100 mum), indicating that the I-h channel subtypes in area postrema cells could be modulated by intracellular cAMP. Our findings indicate that I-h contributes to the subthreshold membrane and firing properties of rat area postrema. neurons and may regulate their resting membrane potential and firing patterns.