Inhibition of constitutive inward rectifier currents in cerebellar granule cells by pharmacological and synaptic activation of GABA receptors

Autor: Paola Rossi, David Gall, Alban de Kerchove d'Exaerde, Vanni Taglietti, Lisa Mapelli, Leda Roggeri, Serge N. Schiffmann, Egidio D'Angelo
Rok vydání: 2006
Předmět:
Cerebellum
Patch-Clamp Techniques
GABAB receptors
Neural Inhibition -- drug effects
Neurons -- drug effects
Receptors
GABA-B -- metabolism
Synaptic Transmission
Membrane Potentials
Receptors
G-Protein-Coupled
GABA Antagonists
Mice
Phosphoprotein Phosphatases
Potassium Channels
Inwardly Rectifying -- metabolism
GABA Agonists -- pharmacology
Neurons
Membrane Potentials -- physiology
GABAA receptor
Inward-rectifier potassium ion channel
General Neuroscience
Phosphoprotein Phosphatases -- metabolism
Synaptic Transmission -- drug effects
Membrane Potentials -- drug effects
Sciences bio-médicales et agricoles
Cell biology
medicine.anatomical_structure
Receptors
GABA-B -- drug effects
Cerebellar Cortex -- metabolism
Phosphoprotein Phosphatases -- antagonists & inhibitors
Inward rectifier
Biology
GABAB receptor
Inhibitory postsynaptic potential
Cerebellar Cortex
Organ Culture Techniques
Receptors
G-Protein-Coupled -- drug effects
medicine
Potassium Channels
Inwardly Rectifying -- drug effects
Non-synaptic plasticity
Animals
Neurons -- metabolism
G protein-coupled inwardly-rectifying potassium channel
Patch clamp
Potassium Channels
Inwardly Rectifying
GABA Agonists
Cerebellar Cortex -- drug effects
Synaptic Transmission -- physiology
Neural Inhibition
Receptors
G-Protein-Coupled -- metabolism
Granule cell
nervous system
Receptors
GABA-B
Neural Inhibition -- physiology
GABA Antagonists -- pharmacology
Neuroscience
Granule cells
Zdroj: European journal of neuroscience, 24 (2
ISSN: 0953-816X
Popis: gamma-Aminobutyric acid (GABA)(B) receptors are known to enhance activation of Kir3 channels generating G-protein-dependent inward rectifier K(+)-currents (GIRK). In some neurons, GABA(B) receptors either cause a tonic GIRK activation or generate a late K(+)-dependent inhibitory postsynaptic current component. However, other neurons express Kir2 channels, which generate a constitutive inward rectifier K(+)-current (CIRK) without requiring G-protein activation. The functional coupling of CIRK with GABA(B) receptors remained unexplored so far. About 50% of rat cerebellar granule cells in the internal granular layer of P19-26 rats showed a sizeable CIRK current. Here, we have investigated CIRK current regulation by GABA(B) receptors in cerebellar granule cells, which undergo GABAergic inhibition through Golgi cells. By using patch-clamp recording techniques and single-cell reverse transcriptase-polymerase chain reaction in acute cerebellar slices, we show that granule cells co-express Kir2 channels and GABA(B) receptors. CIRK current biophysical properties were compatible with Kir2 but not Kir3 channels, and could be inhibited by the GABA(B) receptor agonist baclofen. The action of baclofen was prevented by the GABA(B) receptor blocker CGP35348, involved a pertussis toxin-insensitive G-protein-mediated pathway, and required protein phosphatases inhibited by okadaic acid. GABA(B) receptor-dependent CIRK current inhibition could also be induced by repetitive GABAergic transmission at frequencies higher than the basal autorhythmic discharge of Golgi cells. These results suggest therefore that GABA(B) receptors can exert an inhibitory control over CIRK currents mediated by Kir2 channels. CIRK inhibition was associated with an increased input resistance around rest and caused a approximately 5 mV membrane depolarization. The pro-excitatory action of these effects at an inhibitory synapse may have an homeostatic role re-establishing granule cell readiness under conditions of strong inhibition.
Journal Article
Research Support, Non-U.S. Gov't
FLWIN
info:eu-repo/semantics/published
Databáze: OpenAIRE
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