The Cav 2.1/ 1A (P/Q-Type) Voltage-Dependent Calcium Channel Mediates Inhibitory Neurotransmission onto Mouse Cerebellar Purkinje Cells

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The effects of voltage-dependent calcium channel (VDCC) antagonists on spontaneous inhibitory postsynaptic currents (sIPSCs) in mouse Purkinje cells were examined using in vitro cerebellar slices. The inorganic ion Cd2+ reduced sIPSC amplitude and frequency. No additional block was seen with the Na+ channel antagonist tetrodotoxin (TTX) suggesting that all action potential-evoked inhibitory GABA release was mediated by high-voltage-activated VDCCs. No evidence was found for involvement of Cav1/α1C and α1D (L-type), Cav2.2/α1B (N-type) or Cav2.3/α1E (R-type) high-voltage-activated VDCCs or low-voltage-activated Cav3/α1G, α1H and α1I (T-type) VDCCs in mediating presynaptic GABA release. Blockade of sIPSCs by 200 nmω-agatoxin IVA implicated the Cav2.1/α1A (P/Q-type) subtype of high-voltage-activated VDCCs in mediating inhibitory transmission. Inhibition by ω-agatoxin IVA was similar to that seen with Cd2+ and TTX. Selective antibodies directed against the Cav2.1 subunit revealed staining in regions closely opposed to Purkinje cell somata. Cav2.1 staining was colocalized with staining for antibodies against glutamic acid decarboxylase and corresponded well with the pericellular network formed by GABAergic basket cell interneurons. Antibody labelling of Cav2.3 revealed a region-specific expression. In the cerebellar cortex anterior lobe, Cav2.3 staining was predominantly somatodendritic; whilst in the posterior lobe, perisomatic staining was seen primarily. However, electrophysiological data was not consistent with a role for the Cav2.3 subunit in mediating presynaptic GABA release. No consistent staining was seen for other Cav (α1) subunits. Electrophysiological and immunostaining data support a predominant role for Cav2.1 subunits in mediating action potential-evoked inhibitory GABA release onto mouse Purkinje cells.



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