• GABAergic terminals;
  • hippocampus;
  • intraterminal pH;
  • ion exchanger;
  • miniature inhibitory postsynaptic currents


The effects of pHi on GABAergic miniature inhibitory postsynaptic currents (mIPSCs) were studied in mechanically dissociated CA3 pyramidal neurons, by use of ammonium prepulse and whole-cell patch-clamp techniques, under the voltage-clamp condition. NH4Cl itself, which is expected to alkalinize pHi, increased GABAergic mIPSC frequency in a concentration-dependent manner. In contrast, NH4Cl decreased mIPSC frequency, either in the presence of 200 µm Cd2+ or in Ca2+-free external solution, suggesting that intraterminal alkalosis decreased GABAergic mIPSC frequency while [NH4+] itself may activate Ca2+ channels by depolarizing the terminal. On the other hand, GABAergic mIPSC frequency was greatly increased immediately after NH4Cl removal, a condition expected to acidify pHi, and recovered to the control level within 2 min after NH4Cl removal. This explosive increase in mIPSC frequency observed after NH4Cl removal was completely eliminated after depletion of Ca2+ stores with 1 µm thapsigargin in the Ca2+-free external solution, suggesting that acidification increases in intraterminal Ca2+ concentration via both extracellular Ca2+ influx and Ca2+ release from the stores. However, the acidification-induced increase in mIPSC frequency had not recovered by 10 min after NH4Cl removal either in the Na+-free external solution or in the presence of 10 µm 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), a specific Na+/H+ exchanger (NHE) blocker. The present results suggest that NHEs are major intraterminal pH regulators on GABAergic presynaptic nerve terminals, and that the NHE-mediated regulation of pHi under normal physiological or pathological conditions might play an important role in the neuronal excitability by increasing inhibitory tones.