The Journal of Neuroscience, April 15, 1998, 18(8):2982-2990
Regulation of Presynaptic NMDA Responses by External and
Intracellular pH Changes at Developing Neuromuscular Synapses
Yu-Hwa
Chen1,
Mei-Lin
Wu2, and
Wen-Mei
Fu1
Departments of 1 Pharmacology and
2 Physiology, College of Medicine, National Taiwan
University, Taipei, Taiwan 100, Republic of China
NMDA receptors play important roles in synaptic plasticity and
neuronal development. The functions of NMDA receptors are modulated by
many endogenous substances, such as external pH
(pHe), as well as second messenger systems. In the
present study, the nerve-muscle cocultures of Xenopus
embryos were used to investigate the effects of both external and
intracellular pH (pHi) changes on the functional responses of presynaptic NMDA receptors. Spontaneous synaptic currents
(SSCs) were recorded from innervated myocyte using whole-cell recordings. Local perfusion of NMDA at synaptic regions increased the
SSC frequency via the activation of presynaptic NMDA receptors. A
decrease in pHe from 7.6 to 6.6 reduced NMDA responses to
23% of the control, and an increase in pHe from 7.6 to 8.6 potentiated the NMDA responses in increasing SSC frequency. The effect
of NMDA on intracellular Ca2+ concentration
([Ca2+]i) was also affected by
pHe changes: external acidification inhibited and
alkalinization potentiated [Ca2+]i
increases induced by NMDA. Intracellular pH changes of single soma were
measured by ratio fluorometric method using 2,7-bis (carboxyethyl)-5,6-carboxyfluorescein (BCECF). Cytosolic acidification was used in which NaCl in Ringer's solution was replaced with weak
organic acids. Acetate and propionate but not methylsulfate substitution caused intracellular acidification and potentiated NMDA
responses in increasing SSC frequency, intracellular free Ca2+ concentration, and NMDA-induced currents. On
the other hand, cytosolic alkalinization with NH4Cl did not
significantly affect these NMDA responses. These results suggest that
the functions of NMDA receptors are modulated by both pHe
and pHi changes, which may occur in some physiological or
pathological conditions.
Key words:
NMDA receptor; NMDA-induced current; intracellular
alkalinization; cytosolic acidification; extracellular pH change; developing motoneuron
Copyright © 1998 Society for Neuroscience 0270-6474/98/1882982-09$05.00/0
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