The origin of the post-tetanic hyperpolarization of mammalian motor nerve terminals.

1. Motor nerve terminals in magnesium-poisoned rat hemidiaphragm-phrenic nerve preparations in vitro were stimulated with short depolarizing pulses of approximately threshold strength and the evoked antidromic responses recorded from the phrenic nerve. The percentage of these 1/sec or 0.5/sec stimuli to which there was no antidromic response was used as a quantitative measure of the terminal excitability. After standard tetanic stimulation (1000 impulses at 100/sec) the excitability of the terminals was depressed for an average duration of 60-70 sec, during most of which time no antidromic responses to stimuli of pretetanic intensity were recorded. There was no significant interaction between stimuli to the terminals at rates of 1 or 0.5/sec.2. Potassium-free solutions at first increased, then decreased, the post-tetanic depression of excitability. Raising [K](o) threefold (15 mM) abolished the post-tetanic depression and often converted it to an exaltation of excitability.3. Polarizing currents were applied to the terminals with a second electrode. Depolarizing currents increased, while hyperpolarizing currents decreased, the post-tetanic depression of excitability.4. In solutions with 70% of the normal NaCl content replaced by sucrose, the post-tetanic depression of excitability was reversibly prolonged.5. In the presence of 7.7 x 10(-6)M digoxin or 0.42 mM ouabain there was a small reversible reduction of post-tetanic excitability.6. After exposure to solutions containing no glucose or to solutions containing 3-5 mM sodium azide the excitability of the terminals was not altered by the tetanus. After washing with the control solution, post-tetanic depression of excitability returned. Antimycin-A (1.8 x 10(-6)M) had little or no effect upon post-tetanic excitability.7. It was concluded that the post-tetanic depression of excitability reflected hyperpolarization of the terminals and that this hyperpolarization was caused by a shift of the membrane potential towards the potassium equilibrium potential because of an increase in potassium permeability.