The Na+/H+ exchanger is a major pH regulator in GABAergic presynaptic nerve terminals synapsing onto rat CA3 pyramidal neurons

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,...

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Veröffentlicht in:Journal of neurochemistry 2006-11, Vol.99 (4), p.1224-1236
Hauptverfasser: Jang, Il‐Sung, Brodwick, Malcolm S., Wang, Zhi‐Ming, Jeong, Hyo‐Jin, Choi, Byung‐Ju, Akaike, Norio
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Sprache:eng
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Zusammenfassung: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.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2006.04168.x