The effects of raising intracellular calcium on synaptic GABAA receptor-channels.
The effects of various calcium (Ca2+) loads imposed through whole-cell patch electrodes on dentate gyrus granule cells were investigated on synaptic GABAA receptor-channels. The kinetics of spontaneous inhibitory postsynaptic currents (sIPSCs) were similar when recorded without any exogenous Ca2+ buffers in the patch electrode or with up to 30 mM BAPTA in the pipette. Unbuffered Ca2+ concentrations of 20-100 microM in the patch pipettes induced a gradual prolongation of miniature IPSC (mIPSC) decays over the course of the recording (10-40 min) with no apparent change in their rise times, peak amplitudes, or frequency of occurrence. This effect was not mimicked by other divalent cations such as strontium. Infusion into the cells of free ionic Ca2+ concentrations buffered with various affinity chelators in the pipette had more pronounced effects on synaptic GABAA currents. Free ionic Ca2+ buffered in the range of 200-400 nM with BAPTA prolonged the decay time constant of mIPSCs. Introducing buffered Ca2+ into the neurons in excess of 1 microM, with a relatively low affinity buffer such as Br2BAPTA, resulted in a marked inhibition of mIPSCs. A similar effect was observed following release of Ca2+ from intracellular stores induced by caffeine (10 mM). We conclude that Ca2+ has a biphasic effect on synaptic GABAA receptor-channels. A high affinity potentiation, consistent with a prolongation of channel burst duration, and a low affinity depression of channel activity both contribute to a complex regulation of synaptic GABAA receptors by [Ca2+]i that has a profound bearing on cellular mechanisms of plasticity and pathological alterations in neuronal excitability.
De Koninck
Y
Y
Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada.
Mody
I
I
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D013324:Strontium / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
D002614:Chelating Agents; D007473:Ion Channels; D010726:Phosphodiesterase Inhibitors; D011963:Receptors, GABA-A; D002110:Caffeine; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D013324:Strontium