Negative Shift in the Glycine Reversal Potential Mediated by a Ca2+-Dependent and pH-Dependent Mechanism in Interneurons

Cartwheel cells are glycinergic auditory interneurons which fire Na+ - and Ca2+ - 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 Ca2+ spiking induced by depolarization, thus enhancing glycine's inhibitory effect for similar to 30 s following cessation of spiking. Combined perforated patch electrophysiology and imaging studies showed that the negative E-gly shift was triggered by a Ca2+ -dependent intracellular acidification. The effect on E-gly was likely caused by bicarbonate-Cl- exchanger-mediated reduction in intracellular Cl-, as H2DIDS and removal of HCO3-/CO2 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 Ca2+ -dependent mechanism serves to maintain or enhance the strength of inhibition in the face of increased excitatory activity.