Negative Shift in the Glycine Reversal Potential Mediated by a Ca 2+ - and pH-Dependent Mechanism in Interneurons

Cartwheel cells are glycinergic auditory interneurons which fire Na + - and Ca 2+ -dependent spike bursts, termed complex spikes, and which synapse on both principal cells and one another. The reversal potential for glycine ( E gly ) can be hyperpolarizing or depolarizing in cartwheel cells, and many cells are even excited by glycine. We explored the role of spike activity in determining E gly in mouse cartwheel cells using gramicidin perforated-patch recording. E gly was found to shift toward more negative potentials after a period of complex spiking or Ca 2+ spiking induced by depolarization, thus enhancing glycine's inhibitory effect for ∼30 s following cessation of spiking. Combined perforated patch electrophysiology and imaging studies showed that the negative E gly shift was triggered by a Ca 2+ -dependent intracellular acidification. The effect on E gly was likely caused by bicarbonate-Cl − exchanger-mediated reduction in intracellular Cl − , as H 2 DIDS and removal of HCO 3 − /CO 2 inhibited the negative E gly shift. The outward Cl − flux underlying the negative shift in E gly opposed a positive shift triggered by passive Cl − redistribution during the depolarization. Thus, a Ca 2+ -dependent mechanism serves to maintain or enhance the strength of inhibition in the face of increased excitatory activity.