Pharmacological Analysis of the Activation and Receptor Properties of the Tonic GABACR Current in Retinal Bipolar Cell TerminalsReport as inadecuate




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GABAergic inhibition in the central nervous system CNS can occur via rapid, transient postsynaptic currents and via a tonic increase in membrane conductance, mediated by synaptic and extrasynaptic GABAA receptors GABAARs respectively. Retinal bipolar cells BCs exhibit a tonic current mediated by GABACRs in their axon terminal, in addition to synaptic GABAAR and GABACR currents, which strongly regulate BC output. The tonic GABACR current in BC terminals BCTs is not dependent on vesicular GABA release, but properties such as the alternative source of GABA and the identity of the GABACRs remain unknown. Following a recent report that tonic GABA release from cerebellar glial cells is mediated by Bestrophin 1 anion channels, we have investigated their role in non-vesicular GABA release in the retina. Using patch-clamp recordings from BCTs in goldfish retinal slices, we find that the tonic GABACR current is not reduced by the anion channel inhibitors NPPB or flufenamic acid but is reduced by DIDS, which decreases the tonic current without directly affecting GABACRs. All three drugs also exhibit non-specific effects including inhibition of GABA transporters. GABACR ρ subunits can form homomeric and heteromeric receptors that differ in their properties, but BC GABACRs are thought to be ρ1-ρ2 heteromers. To investigate whether GABACRs mediating tonic and synaptic currents may differ in their subunit composition, as is the case for GABAARs, we have examined the effects of two antagonists that show partial ρ subunit selectivity: picrotoxin and cyclothiazide. Tonic and synaptic GABACR currents were differentially affected by both drugs, suggesting that a population of homomeric ρ1 receptors contributes to the tonic current. These results extend our understanding of the multiple forms of GABAergic inhibition that exist in the CNS and contribute to visual signal processing in the retina.



Author: Stefanie M. Jones, Mary J. Palmer

Source: http://plos.srce.hr/



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