Na+/K+-ATPase Inhibition Partially Mimics the Ethanol-Induced Increase of the Golgi Cell-Dependent Component of the Tonic GABAergic Current in Rat Cerebellar Granule Cells
Figure 9
Proposed circuitry of a Golgi cell-granule cell synapse illustrating the effect of TTX and acute EtOH on GABAergic transmission.
CGNs make synaptic contacts by both glutamatergic Mossy fibers and GABAergic GoC interneurons. These synapses are surrounded by a glial sheath (black dashed line), forming a glomerulus. (A) Under baseline conditions, GoC firing releases GABA into the synaptic space, mediating phasic GABAAR sIPSCs on CGNs (synaptic GABAARs depicted in yellow). There is also a pool of GABA in the extrasynaptic space mediating CGN-Itonic. Spontaneous action potential-dependent GABA release from GoCs contributes to this pool of GABA that activates extrasynaptic GABAARs (depicted in green) – for clarity purposes, perisynaptic receptors are excluded from the illustration. (B) In the presence of TTX, GoC firing ceases, allowing only quantal release of GABA into the synaptic space and significantly reducing phasic GABAAR sIPSCs. Extrasynaptic GABA levels are also reduced, thereby decreasing CGN-Itonic. (C) Acute EtOH inhibits the Na+/K+-ATPase found on GoCs (and possibly also a quinidine-sensitive K+-channel [20]). Inhibition of these membrane proteins depolarizes the membrane potential of GoCs, thereby increasing spontaneous GoC firing and phasic GABA release onto CGNs. This leads to a robust increase in the frequency of phasic GABAAR-mediated sIPSCs and also increases extrasynaptic GABA levels, resulting in an enhancement of CGN-Itonic.