Hsu K S, Liang Y C, Huang C C
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan.
J Neurosci Res. 2000 Nov 1;62(3):403-15. doi: 10.1002/1097-4547(20001101)62:3<403::AID-JNR11>3.0.CO;2-3.
The effects of extracellular acidification on the synaptic function and neuronal excitability were investigated on the hippocampal CA1 neurons. A decrease of extracellular pH from 7.4 to 6.7 did not alter either the resting membrane potential or the neuronal membrane input resistance. Extracellularly recorded field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs) were significantly reduced by acidosis. Additionally, the amplitude of presynaptic fiber volley was also reduced. The sensitivity of postsynaptic neurons to N-methyl-D-aspartate, but not to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, was depressed by acidosis. Lowering of extracellular pH did not significantly affect the magnitude of paired-pulse facilitation (PPF) of synaptic transmission. Acidosis also reversibly limited the sustained repetitive firing (RF) of Na(+)-dependent action potentials elicited by injection of depolarizing current pulses into the pyramidal cells. The limitation of RF by extracellular acidification was accompanied by the reduction of the maximal rate of rise (;V(max)) of the action potentials and the amplitude of afterhyperpolarization. Neither the Na (+)/H (+) antiporter blocker 5-(N -ethyl -N -isopropyl)-amiloride nor the selective adenosine A (1) receptor antagonist 1,3-dipropyl -8-cyclopentylxanthine, however, affected the acidosis -induced synaptic depression. It was also found that acidosis did not affect either the induction r maintenance of long -term potentiation (LTP) at Schaffer collateral -CA 1 synapses. These results suggest that the extracellular acidosis -induced synaptic depression is likely to result from an inhibition of presynaptic Na (+) conductance, thereby decreasing the amplitude of action potentials in individual afferent fibers or the number of afferent fiber activation to stimuli and then indirectly affecting the signaling processes contributing to trigger neurotransmitter release.
在海马CA1神经元上研究了细胞外酸化对突触功能和神经元兴奋性的影响。细胞外pH从7.4降至6.7既未改变静息膜电位，也未改变神经元膜输入电阻。酸中毒显著降低了细胞外记录的场兴奋性突触后电位（fEPSP）和群体峰电位（PS）。此外，突触前纤维群峰电位的幅度也降低了。酸中毒降低了突触后神经元对N-甲基-D-天冬氨酸的敏感性，但对α-氨基-3-羟基-5-甲基异恶唑-4-丙酸的敏感性未产生影响。细胞外pH的降低对突触传递的双脉冲易化（PPF）幅度没有显著影响。酸中毒还可逆地限制了通过向锥体细胞注入去极化电流脉冲引发的Na⁺依赖性动作电位的持续重复放电（RF）。细胞外酸化对RF的限制伴随着动作电位最大上升速率（Vmax）和超极化后电位幅度的降低。然而，Na⁺/H⁺反向转运体阻滞剂5-（N-乙基-N-异丙基）氨氯吡咪和选择性腺苷A₁受体拮抗剂1,3-二丙基-8-环戊基黄嘌呤均未影响酸中毒诱导的突触抑制。还发现酸中毒对Schaffer侧支-CA1突触处长期增强（LTP）的诱导或维持均无影响。这些结果表明，细胞外酸中毒诱导的突触抑制可能是由于突触前Na⁺电导受到抑制，从而降低了单个传入纤维动作电位的幅度或对刺激的传入纤维激活数量，进而间接影响了有助于触发神经递质释放的信号传导过程。
