The effects of pH changes on the frequency of miniature end‐plate potentials at the frog neuromuscular junction.

Abstract

As reported by Landau and Nachshen, a decrease in extracellular pH at the frog [Rana pipiens] neuromuscular junction led to an increase in MEPP [miniature endplate potential] frequency. Decreasing the extracellular pH still increased the MEPP frequency when the bathing Ringer contains 10 mM Ca2+, in place of the usual 2.5 mM. At the mammalian neuromuscular junction, the elevated Ca2+ blocks the effect of the pH change on the MEPP frequency. In Cl--free solution (isethionate or methylsulfate substitution) MEPP frequency was no longer a monotonic function of decreasing pH. Instead there was an optimum pH for spontaneous release between pH 6.6 and 8.6. In Cl- containing Ringer MEPP frequency may increase with increasing extracellular acidity because there is a change in the P[permeability]Cl of the nerve terminal leading to a depolarization. In agreement with this idea, in low Ca2+ Ringer, acid pH had little effect on the MEPP frequency. Decreasing the intracellular pH by raising P[partial pressure]CO2 produced substantial increases in the MEPP frequency. The effects were much greater than the effects of equal changes of H+ in the extracellular solution. Possible explanations for the effects of increased PCO2 were discussed. Although release of Ca2+ from mitochondria or other unknown effects of intracellular pH change or molecular CO2 are possible, an important step in transmitter release probably involves an electrostatic repulsion between fixed membrane surface charges on the transmitter containing vesicles and the inner face of the nerve terminal. The surface charge density would be decreased by a lower pH in the axoplasm, and this would increase the rate of spontaneous transmitter release, in agreement with the observations.