Wellner-Kienitz M C, Shams H, Scheid P
Institut für Physiologie, Ruhr-Universität Bochum, 44780 Bochum, Germany.
J Neurophysiol. 1998 Jun;79(6):2885-94. doi: 10.1152/jn.1998.79.6.2885.
Neurons in fetal rat medullary slices that exhibited spontaneous electrical activity after blockade of synaptic transmission were investigated for their response to decreases in extracellular pH. Increases in [H+] (induced either by fixed acid or increases in PCO2) induced a significant increase in the frequency of action potentials, associated with a membrane depolarization, and/or increases in the slope of the interspike depolarization. In addition, CO2/H+ prolonged the repolarizing phase of action potentials and reduced the afterhyperpolarization, suggesting that K+ channels were the primary site of CO2/H+ action. The type of K+ channel that was modulated by CO2/H+ was identified by application of agents that inhibited Ca2+-activated K+ channels either directly (tetraethylammonium chloride, TEA) or indirectly (Cd2+ ions) by inhibiting Ca2+ influx. CO2/H+ effects on neuronal activity were abolished after application of these blockers. The contribution of Ca2+-activated K+ channels to H+ sensitivity of these neurons was confirmed further in voltage-clamp experiments in which outward rectifying I-V curves were recorded that revealed a zero current potential of -70 mV. CO2/H+ induced a prominent reduction in outward currents and shifted the zero current potential to more positive membrane potentials (mean -63 mV). The CO2/H+-sensitive current reversed at -72 mV and was blocked by external application of TEA. It is concluded that CO2/H+ exerts its stimulatory effects on fetal medullary neurons by inhibition of Ca2+-activated K+ channels, either directly or indirectly, by blocking voltage-dependent Ca2+ channels, which in turn results in a reduction of K+ efflux and in cell depolarization.
对突触传递被阻断后表现出自发电活动的胎鼠延髓切片中的神经元，研究了它们对细胞外pH降低的反应。[H⁺]升高（由固定酸或PCO₂升高诱导）导致动作电位频率显著增加，伴有膜去极化和/或峰间去极化斜率增加。此外，CO₂/H⁺延长了动作电位的复极化阶段并减少了超极化后电位，表明钾通道是CO₂/H⁺作用的主要位点。通过应用直接（氯化四乙铵，TEA）或间接（Cd²⁺离子）抑制钙内流从而抑制钙激活钾通道的药物，确定了被CO₂/H⁺调节的钾通道类型。应用这些阻滞剂后，CO₂/H⁺对神经元活动的影响被消除。在电压钳实验中进一步证实了钙激活钾通道对这些神经元氢离子敏感性的贡献，在该实验中记录到外向整流I-V曲线，显示零电流电位为-70 mV。CO₂/H⁺导致外向电流显著减少，并将零电流电位转移到更正的膜电位（平均-63 mV）。CO₂/H⁺敏感电流在-72 mV处反转，并被外部应用的TEA阻断。得出的结论是，CO₂/H⁺通过直接或间接抑制钙激活钾通道，阻断电压依赖性钙通道，从而对胎鼠延髓神经元发挥刺激作用，这反过来导致钾外流减少和细胞去极化。
