Han Jin-Eon, Cho Jin-Hwa, Choi In-Sun, Kim Do-Yeon, Jang Il-Sung
Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea.
Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea.; Brain Science & Engineering Institute, Kyungpook National University, Daegu 41940, Korea.
Korean J Physiol Pharmacol. 2017 Mar;21(2):215-223. doi: 10.4196/kjpp.2017.21.2.215. Epub 2017 Feb 21.
The effects of acidic pH on several voltage-dependent ion channels, such as voltage-dependent K and Ca channels, and hyperpolarization-gated and cyclic nucleotide-activated cation (HCN) channels, were examined using a whole-cell patch clamp technique on mechanically isolated rat mesencephalic trigeminal nucleus neurons. The application of a pH 6.5 solution had no effect on the peak amplitude of voltage-dependent K currents. A pH 6.0 solution slightly, but significantly inhibited the peak amplitude of voltage-dependent K currents. The pH 6.0 also shifted both the current-voltage and conductance-voltage relationships to the depolarization range. The application of a pH 6.5 solution scarcely affected the peak amplitude of membrane currents mediated by HCN channels, which were profoundly inhibited by the general HCN channel blocker Cs (1 mM). However, the pH 6.0 solution slightly, but significantly inhibited the peak amplitude of HCN-mediated currents. Although the pH 6.0 solution showed complex modulation of the current-voltage and conductance-voltage relationships, the midpoint voltages for the activation of HCN channels were not changed by acidic pH. On the other hand, voltage-dependent Ca channels were significantly inhibited by an acidic pH. The application of an acidic pH solution significantly shifted the current-voltage and conductance-voltage relationships to the depolarization range. The modulation of several voltage-dependent ion channels by an acidic pH might affect the excitability of mesencephalic trigeminal nucleus neurons, and thus physiological functions mediated by the mesencephalic trigeminal nucleus could be affected in acidic pH conditions.
利用全细胞膜片钳技术,在机械分离的大鼠中脑三叉神经核神经元上,研究了酸性pH对几种电压依赖性离子通道的影响,这些通道包括电压依赖性钾通道和钙通道,以及超极化激活的环核苷酸门控阳离子(HCN)通道。应用pH 6.5的溶液对电压依赖性钾电流的峰值幅度没有影响。pH 6.0的溶液轻微但显著地抑制了电压依赖性钾电流的峰值幅度。pH 6.0还使电流-电压关系和电导-电压关系都向去极化范围偏移。应用pH 6.5的溶液几乎不影响由HCN通道介导的膜电流的峰值幅度,而一般的HCN通道阻滞剂铯(1 mM)可显著抑制该电流。然而,pH 6.0的溶液轻微但显著地抑制了HCN介导电流的峰值幅度。尽管pH 6.0的溶液对电流-电压关系和电导-电压关系表现出复杂的调制作用,但酸性pH并未改变HCN通道激活的中点电压。另一方面,电压依赖性钙通道受到酸性pH的显著抑制。应用酸性pH溶液可使电流-电压关系和电导-电压关系显著向去极化范围偏移。酸性pH对几种电压依赖性离子通道的调制可能会影响中脑三叉神经核神经元的兴奋性,因此在酸性pH条件下,中脑三叉神经核介导的生理功能可能会受到影响。