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Sandoz Institute for Medical Research, London.

1. The responses of adult and neonatal rat dorsal root ganglion (DRG) neurones to buffered acidic solutions were studied with both voltage clamp and radioactive ion flux techniques. Electrophysiological experiments were made on acutely isolated neurones and ion flux experiments were made on cells that had been in culture for 3-6 days. 2. Acid solutions of pH < 6.2 evoked a sustained, slowly inactivating inward current in neurones voltage clamped at negative holding potentials. The size of the current increased with increasing proton concentrations. This response was restricted to a sub-population (approximately 45%) of adult and neonatal rat DRG neurones and was distinct from a rapidly activating and inactivating proton-induced inward sodium current that was also found in DRG neurones. 3. The proton-activated sustained current was due to an increase in cation conductance that allowed K+, Cs+ and Na+ to pass with PK/PNa = 1.32 and PCs/PNa = 1.12. 4. Radioactive ion efflux experiments made on neonatal rat cultured DRG neurones showed that protons also increased the permeability to both [14C]guanidinium and 86Rb+ ions. The half-maximal increase in efflux rate for 86Rb+ occurred at pH 5.8. Acid solution also stimulated the efflux of 86Rb+ in cultures of adult rat neurones. 5. Cells that showed a late, sustained proton-activated current also responded to capsaicin. In addition, no proton-activated fluxes of either [14C]guanidinium or 86Rb+ ions were observed in cultures of DRG neurones that had been treated with high concentrations of capsaicin (10 microM) to kill the capsaicin-sensitive neurones. Thus this proton-activated current is restricted largely, if not exclusively, to capsaicin-sensitive peripheral sensory neurones.

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