Negative shift in the glycine reversal potential mediated by a Ca2+- 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 approximately 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.
Kim
Yuil
Y
Neuroscience Graduate Program, Oregon Health & Science University, Portland, Oregon 97239, USA.
Trussell
Laurence O
LO
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001578:Benzopyrans / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D001703:Biophysics; D002118:Calcium / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D017626:Cochlear Nucleus / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology*; D018684:Glycine Agents / Q000494:pharmacology*; D006531:HEPES / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D018408:Patch-Clamp Techniques / Q000379:methods; D011810:Quinoxalines / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001578:Benzopyrans; D001639:Bicarbonates; D002712:Chlorides; D018691:Excitatory Amino Acid Antagonists; D018684:Glycine Agents; D011810:Quinoxalines; C063917:SNARF dye; D026941:Sodium Channel Blockers; D027982:Sodium-Bicarbonate Symporters; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; D006531:HEPES; D002118:Calcium; D005998:Glycine