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Distinctive glycinergic currents with fast and slow kinetics in thalamus
Amer A Ghavanini1, David A Mathers, Hee-Soo Kim
1Department of Anesthesiology, Pharmacology, and Therapeutics, The University of British Columbia, Vancouver, Canada.
Abstract:
We examined functional properties of inhibitory postsynaptic currents (IPSCs) evoked by medial lemniscal stimulation, spontaneous IPSCs (sIPSCs), and single-channel, extrasynaptic currents evoked by glycine receptor agonists or gamma-aminobutyric acid (GABA) in rat ventrobasal thalamus. We identified synaptic currents by reversal at E(Cl) and sensitivity to elimination by strychnine, GABA(A) antagonists, or combined application. Glycinergic IPSCs featured short (about 12 ms) and long (about 80 ms) decay time constants. These fast and slow IPSCs occurred separately with monoexponential decays, or together with biexponential decay kinetics. Glycinergic sIPSCs decayed monoexponentially with time constants, matching fast and slow IPSCs. These findings were consistent with synaptic responses generated by two populations of glycine receptors, localized under different nerve terminals. Glycine, taurine, or beta-alanine applied to excised membrane patches evoked short- and long-duration current bursts. Extrasynaptic burst durations resembled fast and slow IPSC time constants. The single, intermediate time constant (about 22 ms) of GABA(A)ergic IPSCs cotransmitted with glycinergic IPSCs approximated the burst duration of extrasynaptic GABA(A) channels. We noted differences between synaptic and extrasynaptic receptors. Endogenously activated glycine and GABA(A) receptor channels had higher Cl- permeability than that of their extrasynaptic counterparts. The beta-amino acids activated long-duration bursts at extrasynaptic glycine receptors, consistent with a role in detection of ambient taurine or beta-alanine. Heterogeneous kinetics and permeabilities implicate molecular and functional diversity in thalamic glycine receptors. Fast, intermediate, and slow inhibitory postsynaptic potential decays, mostly attributed to cotransmission by glycinergic and GABAergic pathways, allow for discriminative modulation and integration with voltage-dependent currents in ventrobasal neurons.
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