I. S. Jang and M. S. Brodwick contributed equally to this work.
The Na+/H+ exchanger is a major pH regulator in GABAergic presynaptic nerve terminals synapsing onto rat CA3 pyramidal neurons
Article first published online: 14 AUG 2006
Journal of Neurochemistry
Volume 99, Issue 4, pages 1224–1236, November 2006
How to Cite
Jang, I.-S., Brodwick, M. S., Wang, Z.-M., Jeong, H.-J., Choi, B.-J. and Akaike, N. (2006), The Na+/H+ exchanger is a major pH regulator in GABAergic presynaptic nerve terminals synapsing onto rat CA3 pyramidal neurons. Journal of Neurochemistry, 99: 1224–1236. doi: 10.1111/j.1471-4159.2006.04168.x
- Issue published online: 14 AUG 2006
- Article first published online: 14 AUG 2006
- Received February 16, 2006; revised manuscript received June 3, 2006; accepted July 16, 2006.
- GABAergic terminals;
- 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.