Lee J, Taira T, Pihlaja P, Ransom B R, Kaila K
Department of Biosciences, University of Helsinki, Finland.
Brain Res. 1996 Jan 15;706(2):210-6. doi: 10.1016/0006-8993(95)01214-1.
It is generally known that hyperventilation produces an increase in neuronal excitability. However, the mechanism whereby a change in CO2 partial pressure (PCO2) leads to changes in neural excitability is not known. We have studied this phenomenon in rat hippocampal slices using double-barrelled microelectrodes for simultaneous recording of field excitatory postsynaptic potentials (EPSPs) and extracellular pH in stratum radiatum of area CA1. A drop in PCO2 from the control level, 36 mmHg to 7 mmHg, produced an increase in extracellular pH of 0.4-0.6 pH units and a transient increase in EPSP slope by about 20-30%. Despite the stable extracellular alkalosis, the EPSP reverted back to its original level within 10 min. Switching back to 36 mmHg PCO2 restored the original extracellular pH and caused a transient decrease in the EPSP slope. Pharmacological blockade of NMDA receptor and/or GABAA receptor had no influence on the effects of CO2. An increase in PCO2 to 145 mmHg led to a stable fall in extracellular pH by 0.6 units and to a transient 30-50% decrease in EPSP slope. The above results indicate that the CO2-induced changes in neuronal excitability were not caused by changes in extracellular pH but they might have been mediated by changes in intracellular pH. Indeed, exposing the slices to the permeant weak base, trimethylamine (20 mM), which is known to produce a rise in intracellular pH, increased the EPSP slope by 50-70%. Application of 20 mM propionate (a permeant weak acid) decreased the EPSP slope by 40-60%. We conclude that the transient changes in the EPSP seen in response to changes in PCO2 are mediated by in intracellular pH.
众所周知，过度通气会导致神经元兴奋性增加。然而，二氧化碳分压（PCO2）的变化导致神经兴奋性改变的机制尚不清楚。我们使用双管微电极在大鼠海马切片中研究了这一现象，以同时记录CA1区辐射层的场兴奋性突触后电位（EPSP）和细胞外pH值。PCO2从对照水平36 mmHg降至7 mmHg，导致细胞外pH值升高0.4 - 0.6个pH单位，EPSP斜率短暂增加约20 - 30%。尽管细胞外碱中毒持续存在，但EPSP在10分钟内恢复到原始水平。将PCO2恢复到36 mmHg可使细胞外pH值恢复到原始水平，并导致EPSP斜率短暂下降。NMDA受体和/或GABAA受体的药理学阻断对二氧化碳的作用没有影响。将PCO2增加到145 mmHg导致细胞外pH值稳定下降0.6个单位，EPSP斜率短暂下降30 - 50%。上述结果表明，二氧化碳诱导的神经元兴奋性变化不是由细胞外pH值的变化引起的，而是可能由细胞内pH值的变化介导的。事实上，将切片暴露于渗透性弱碱三甲胺（20 mM）中，已知其会导致细胞内pH值升高，使EPSP斜率增加50 - 70%。应用20 mM丙酸盐（一种渗透性弱酸）使EPSP斜率降低40 - 60%。我们得出结论，响应PCO2变化而观察到的EPSP的短暂变化是由细胞内pH值介导的。
