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The Na + /H + exchanger is a major pH regulator in GABAergic presynaptic nerve terminals synapsing onto rat CA3 pyramidal neurons
Author(s) -
Jang IlSung,
Brodwick Malcolm S.,
Wang ZhiMing,
Jeong HyoJin,
Choi ByungJu,
Akaike Norio
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04168.x
Subject(s) - chemistry , gabaergic , biophysics , amiloride , ionophore , patch clamp , bafilomycin , membrane potential , depolarization , biochemistry , sodium , biology , membrane , apoptosis , receptor , organic chemistry , autophagy
The effects of pH i 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. NH 4 Cl itself, which is expected to alkalinize pH i , increased GABAergic mIPSC frequency in a concentration‐dependent manner. In contrast, NH 4 Cl decreased mIPSC frequency, either in the presence of 200 µ m Cd 2+ or in Ca 2+ ‐free external solution, suggesting that intraterminal alkalosis decreased GABAergic mIPSC frequency while [NH4 + ] itself may activate Ca 2+ channels by depolarizing the terminal. On the other hand, GABAergic mIPSC frequency was greatly increased immediately after NH 4 Cl removal, a condition expected to acidify pH i , and recovered to the control level within 2 min after NH 4 Cl removal. This explosive increase in mIPSC frequency observed after NH 4 Cl removal was completely eliminated after depletion of Ca 2+ stores with 1 µ m thapsigargin in the Ca 2+ ‐free external solution, suggesting that acidification increases in intraterminal Ca 2+ concentration via both extracellular Ca 2+ influx and Ca 2+ release from the stores. However, the acidification‐induced increase in mIPSC frequency had not recovered by 10 min after NH 4 Cl removal either in the Na + ‐free external solution or in the presence of 10 µ m 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 pH i under normal physiological or pathological conditions might play an important role in the neuronal excitability by increasing inhibitory tones.