Prolonged post-tetanic depolarization of frog dorsal root fibers

Abstract In the isolated frog spinal cord, tetanic stimulation of a dorsal root resulted in a sustained negative potential recorded from that root. This negative potential was followed by a large (5–12 mV) and slow (5–60 s) negative after-potential which persisted after the train of impulses and which was succeeded by a long-lasting positive potential. The negative after-potential was postulated to be largely a consequence of excess extracellular K + accumulated during the tetanus, because the negative after-potential and the extracellular [K + ] measured with K + -sensitive microelectrodes were a function of the stimulating current, the stimulation frequency and the duration of the tetanus. Both measures were augmented by procedures which interfered with the clearance of K + from the extracellular space (addition of dinitrophenol or ouabain, partial substitution of Li + for Na + , elimination of K + from the superfusate and cooling). The negative after-potential and the liberation of much of the excess extracellular K + were reduced by increasing the superfusing divalent ion concentration with 4mM Ca 2+ or 50–100 μM Mn 2+ . Both measures were augmented in low Ca 2+ -containing Ringer's solution. The results with low concentrations of Ca 2+ , Na + and K + and with high concentrations of Ca 2+ indicate that the negative after-potential was not caused by a conductance increase for these cations. Reduction of extracellular [Cl − ] did not change the negative after-potential making it unlikely that this anion is a factor in its production. The negative after-potential was not mediated by γ-aminobutyrate because its amplitude and duration were increased by the γ-aminobutyrate antagonist picrotoxin, and were reduced by pentobarbital which enhances the actions of γ-aminobutyrate. Application of the excitatory amino acid antagonists dl -α-aminoadipic acid and glutamic acid diethylester eliminated the negative after-potential and markedly reduced the amount of K + liberated by a tetanus. These results suggest that the K + release that produces the negative after-potential may result from the action of an excitatory amino acid such as l -glutamate or l -aspartate either synaptically released or released from nonsynaptic regions of afferent fibers.