Effects of pH, changes in potassium concentration and metabolic inhibitors on the after-potentials of mammalian non-medullated nerve fibres

The long lasting changes in membrane potential following repetitive stimulation of three types of mammalian nerves consisting predominantly of non-medullated fibres (rabbit and rat cervical sympathetic and cat hypogastric nerves) have been studied in vitro, using nerves suspended in liquid paraffin and with the sucrose-gap technique.2. In Krebs solution (pH 7.4), the post-tetanic change in membrane potential is variable from one nerve to the next. On changing to a solution of acid pH (6.4) however, repetitive excitation is always followed by high voltage positivity. This « acid » effect does not reach its maximum immediately and reasons are given for believing that the delay is attributable to the time taken for hydrogen ions to penetrate the membrane. The « acid » effect is irreversible.3. The post-tetanic positivity of a nerve in acid medium is increased by potassium-free solutions but abolished by inhibitors of intermediate metabolism (iodoacetate, cyanide, azide, 2 : 4 dinitrophenol).4. These observations can be explained by supposing the post-tetanic positivity to be due to stimulation, by the sodium ions which enter the fibres during the tetanus, of an electrogenic ionic pump.5. After a tetanus an isolated stimulus provokes a spike followed by greatly enhanced post-spike negativity and late positivity. This phenomenon is independent both of the reaction of the medium (within the limits pH 5 to 9) and of the sense and degree of change in the membrane potential. The post-tetanic enhancement of post-spike potentials is, however, abolished if the ionic pump mechanism is interrupted.6. Although its origin remains obscure, this post-tetanic enhancement of post-spike potentials is probably of physiological significance since there are reasons for believing that it accounts for post-tetanic facilitation of junctional transmission at the nerve-muscle junction and also perhaps at the autonomic ganglionic relay and the central nervous synapse.