GLYCINE-ACTIVATED CURRENTS ARE CHANGED BY COINCIDENT MEMBRANE DEPOLARIZATION IN DEVELOPING RAT AUDITORY BRAIN-STEM NEURONS

1. During early ontogeny, glycine receptors (GlyRs) exert depolarizing responses which may be of developmental relevance. We have used the g ramicidin-perforated patch technique to elucidate the mechanism of gly cine-activated currents in developing neurones of the rat lateral supe rior olive (LSO). 2. When the holding potential was set to -60 mV, per forated-patch recordings revealed glycine-induced inward currents in 5 9%, outward currents in 5% and biphasic currents in 34% of the LSO neu rones tested (n = 44). The biphasic currents were characterized by a t ransient outward phase which was followed by an inward phase. 3. Ion s ubstitution experiments showed that both Cl- and HCO3- contributed to the glycine-induced biphasic current responses. 4. In the biphasic res ponses, the reversal potential of the glycine-induced current (E-gly) depended on the response phase. A strong shift of E-gly from a mean of -72 mV during the outward phase of the glycine response to a mean of -51 mV during the inward phase was observed, suggesting a shift of an ion gradient. 5. When the membrane potential was depolarized, 'tail' c urrents were induced in the presence of glycine. An increased duration or amplitude of the evoked depolarizations resulted in a proportional enlargement of these tail currents, indicating that they were produce d by a shift of an ion gradient. Since changes of the HCO3- gradient a re negligible, because of the carbonic anhydrase activity, we suggest that these tail currents were caused by a shift of the Cl- gradient. 6 . We conclude that Cl- accumulates intracellularly during the activati on of GlyRs and, consequently, E-gly moves towards more positive value s. 7. Coincident depolarizing stimuli enhanced intracellular Cl- accum ulation and the shift of E-gly, thereby switching hyperpolarizing to d epolarizing action. This change could assist in an activity-dependent strengthening and refinement of glycinergic synapses during the matura tion of inhibitory connectivity.