The Journal of Neurophysiology Vol. 77 No. 4 April 1997, pp. 1844-1852
Copyright ©1997 The American Physiological Society

GABA- and Glycine-Mediated Fall of Intracellular pH in Rat Medullary Neurons In Situ

Mark Lückermann, Stefan Trapp, and Klaus Ballanyi

II. Physiologisches Institut, Universität Göttingen, D-37073 Göttingen, Germany

Lückermann, Mark, Stefan Trapp, and Klaus Ballanyi. GABA- and glycine-mediated fall of intracellular pH in rat medullary neurons in situ. J. Neurophysiol. 77: 1844-1852, 1997. In the region of the ventral respiratory group in brain stem slices from neonatal rats, intracellular pH (pH_i) and membrane currents (I_m) or potentials were measured in neurons dialyzed with the pH-sensitive dye 2,7-bis-carboxyethyl-5(6)-carboxyfluorescein. Currents and increases in membrane conductance (g_m) during bath application of 0.1 or 1 mM -aminobutyric acid (GABA) were accompanied by a delayed mean fall of pH_i by 0.17 and 0.25 pH units, respectively, from a pH_i baseline of 7.33. These effects were reversibly suppressed by 50-100 µM bicuculline. Similar effects on I_m, g_m, and pH_i were revealed on administration of 0.1 or 1 mM glycine. These responses were abolished by 10-100 µM strychnine. Dialysis of the cells with 15-30 µM carbonic anhydrase led to an acceleration of the kinetics and a potentiation of the GABA-induced pH_i decrease. GABA- and glycine-evoked pH_i decreases were very similar during recordings with either high- or low-Cl patch electrodes, although the reversal potential of the accompanying currents differed by ~60 mV. The GABA-induced pH_i decrease, but not the accompanying I_m and g_m responses, was suppressed in CO₂/HCO₃-free, N-2-hydroxy-ethylpiperazine-N-2-ethane sulphonic acid pH-buffered solution. Depolarization from 60 to +30 mV resulted in a sustained fall of pH_i by maximally 0.5 pH units. In this situation, the GABA-induced fall of pH_i turned into an intracellular alkalosis of 0.09-0.15 pH units. The results confirm and extend previous findings obtained in vivo that GABA- or glycine-induced intracellular acidosis of respiratory neurons is due to efflux of HCO₃ via the receptor-coupled Cl channel.

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