Pentobarbital and the effects of GABA and K + on primary afferent terminals

Abstract

Barbiturates prolong (and at times increase) primary afferent depolarization (PAD), the mechanism is unknown. Sucrose gap recordings from the dorsal roots (DR) of frog spinal cords were used to clarify this problem. Addition of pentobarbital (PB) to the superfusate (10 −5 − 2× 10 −4 M) increased the duration of dorsal root potentials (DRP's) generated by DR (DR-DRP) and ventral root (VR-DRP) stimulation. The DR-DRP amplitude increased slightly while the VR-DRP amplitude increased significantly after a 10 min exposure to PB (10 −4 M); then upon continued PB application both potentials declined to below control levels. DR responses to repeated applications of GABA (10 −3 M) and to elevated [K +](10 mM) showed an immediate increase in the response amplitude followed by a progressive decrease. The initial increase in the GABA response, but not the [K +] response, was also observed after prolonged application of PB. PB increased the duration of GABA, but not K +, depolarizations. PB reduced and prolonged the DRP produced by a tetanic stimulus and the focal potential recorded in the dorsal horn. Exposure to PB (10 −4 − 2× 10 −4 M; 10,90 min) did not change the high affinity uptake or spontaneous release of [ 3H]GABA. The K +-evoked [ 3H]GABA release was significantly decreased by PB (5×10 −5 − 2× 10 −4 M). PB appears to act postsynaptically at the Cl − conductance channel and presynaptically by reducing transmitter release.