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High-Voltage-Activated (HVA) Ca(2+) channels are known regulators of synapse formation and transmission and play fundamental roles in neuronal pathophysiology. Small GTPases of Rho and RGK families, via their action on both cytoskeleton and Ca(2+) channels are key molecules for these processes. While the effects of RGK GTPases on neuronal HVA Ca(2+) channels have been widely studied, the effects of RhoA on the HVA channels remains however elusive. Using heterologous expression in Xenopus laevis oocytes, we show that RhoA activity reduces Ba(2+) currents through CaV2.1, CaV2.2 and CaV2.3 Ca(2+) channels independently of CaVβ subunit. This inhibition occurs independently of RGKs activity and without modification of biophysical properties and global level of expression of the channel subunit. Instead, we observed a marked decrease in the number of active channels at the plasma membrane. Pharmacological and expression studies suggest that channel expression at the plasma membrane is impaired via a ROCK-sensitive pathway. Expression of constitutively active RhoA in primary culture of spinal motoneurons also drastically reduced HVA Ca(2+) current amplitude. Altogether our data revealed that HVA Ca(2+) channels regulation by RhoA might govern synaptic transmission during development and potentially contribute to pathophysiological processes when axon regeneration and growth cone kinetics are impaired.

Original publication

DOI

10.1016/j.neuropharm.2015.05.019

Type

Journal article

Journal

Neuropharmacology

Publication Date

10/2015

Volume

97

Pages

201 - 209

Keywords

BAPTA (PubChem CID: 104751), Blebistatin (PubChem CID: 3476986), Brefeldin A (PubChem CID: 5287620), Chloroquine (PubChem CID: 2719), Dynasore (PubChem CID: 5717066), Fasudi (PubChem CID: 3547), MG132 (PubChem CID: 462382), Membrane expression, Motorneurons, ROCK kinase, TEACl (PubChem CID: 5413), Voltage-clamp, Y27632 (PubChem CID: 448042), Animals, Barium, Calcium, Calcium Channels, N-Type, Cations, Cell Membrane, Cells, Cultured, Electroporation, Membrane Potentials, Mice, Transgenic, Motor Neurons, Oocytes, Patch-Clamp Techniques, Spinal Cord, Xenopus laevis, rho GTP-Binding Proteins, rho-Associated Kinases