Negative shift in the glycine reversal potential mediated by a Ca 2+- and pH-dependent mechanism in interneurons

Abstract

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 (Egly) 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 Egly in mouse cartwheel cells using gramicidin perforated-patch recording. Egly 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 Egly shift was triggered by a Ca2+-dependent intracellular acidification. The effect on Egly was likely caused by bicarbonate-Cl- exchanger-mediated reduction in intracellular Cl -, as H2DIDS and removal of HCO3-/CO2 inhibited the negative Egly shift. The outward Cl- flux underlying the negative shift in Egly 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. Copyright © 2009 Society for Neuroscience.