The Journal of Neuroscience, September 16, 2009, 29(37):11495-11510; doi:10.1523/JNEUROSCI.1086-09.2009
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Cellular/Molecular
Negative Shift in the Glycine Reversal Potential Mediated by a Ca2+- and pH-Dependent Mechanism in Interneurons
Yuil Kim1 and
Laurence O. Trussell2
1Neuroscience Graduate Program, Oregon Health & Science University, and 2Oregon Hearing Research Center/Vollum Institute, Portland, Oregon 97239
Correspondence should be addressed to Laurence O. Trussell, 3181 SW Sam Jackson Park Road, L335A Portland, OR 97239. Email: trussell{at}ohsu.edu
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 Ca2+ 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 HCO
/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.
Received March 4, 2009;
revised Aug. 3, 2009;
accepted Aug. 5, 2009.
Correspondence should be addressed to Laurence O. Trussell, 3181 SW Sam Jackson Park Road, L335A Portland, OR 97239. Email: trussell{at}ohsu.edu