Funahashi Makoto, Mitoh Yoshihiro, Kohjitani Atsushi, Matsuo Ryuji
Department of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8525, Japan.
J Physiol. 2003 Oct 1;552(Pt 1):135-48. doi: 10.1113/jphysiol.2003.047191. Epub 2003 Aug 1.
To clarify the functional properties of the hyperpolarization-activated cation current (Ih) as a pacemaker current in area postrema neurons, whole-cell recordings were made in visually identified cells in rat brain slices. The activation of Ih was identified in approximately 62 % of area postrema neurons tested. The cells displaying Ih showed a depolarizing "sag" in responses to hyperpolarizing current injection in current-clamp mode. The reversal potential for the Ih 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 microM), a potent selective Ih channel antagonist, blocked Ih and induced a membrane potential hyperpolarization, suggesting the sustained activation of Ih near the resting potential and a contribution from Ih 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 afterhyperpolarization or action potential waveforms. Ih stabilized the latency of rebound action potentials. Ih was weakly activated by external 8-bromoadenosine 3',5' cyclic monophosphate (1 mM) or forskolin (50-100 microM), indicating that the Ih channel subtypes in area postrema cells could be modulated by intracellular cAMP. Our findings indicate that Ih contributes to the subthreshold membrane and firing properties of rat area postrema neurons and may regulate their resting membrane potential and firing patterns.
为阐明延髓后区神经元中作为起搏电流的超极化激活阳离子电流（Ih）的功能特性，在大鼠脑片的视觉识别细胞中进行了全细胞记录。在所测试的约62%的延髓后区神经元中鉴定出了Ih的激活。显示Ih的细胞在电流钳模式下对超极化电流注入的反应中表现出去极化“下垂”。Ih的反转电位为-36 mV，这表明它取决于细胞外Na+和K+离子的浓度。细胞外Cs+离子（2 mM）和ZD7288（100 μM），一种有效的选择性Ih通道拮抗剂，阻断Ih并诱导膜电位超极化，提示Ih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Ba2+离子导致膜电位去极化，提示内向整流K+电流被阻断。ZD7288通过延长两个动作电位之间的缓慢去极化来降低自发放电率，对后超极化幅度或动作电位波形的影响最小。Ih稳定了反弹动作电位的潜伏期。Ih被细胞外8-溴腺苷3',5'-环磷酸（1 mM）或福斯可林（50-100 μM）微弱激活，表明延髓后区细胞中的Ih通道亚型可被细胞内cAMP调节。我们的研究结果表明，Ih对大鼠延髓后区神经元的阈下膜特性和放电特性有贡献，并可能调节其静息膜电位和放电模式。
