title: Regulation of neuronal high-voltage activated Ca(V)2 Ca(2+) channels by the small GTPase RhoA.
abstract: 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.
authors.affiliation: IBMM, CNRS UMR 5247, Université de Montpellier, 1919 route de Mende, 34293 Montpellier, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Rousset
authors.affiliation: IBMM, CNRS UMR 5247, Université de Montpellier, 1919 route de Mende, 34293 Montpellier, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Cens
authors.affiliation: IBMM, CNRS UMR 5247, Université de Montpellier, 1919 route de Mende, 34293 Montpellier, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Menard
authors.affiliation: Institut des Neurosciences, INSERM U1051, 80 rue Augustin Fliche, 34091 Montpellier, France.
authors.forename: Melissa
authors.initials: M
authors.lastname: Bowerman
authors.affiliation: IBMM, CNRS UMR 5247, Université de Montpellier, 1919 route de Mende, 34293 Montpellier, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Bellis
authors.affiliation: Department of Natural Sciences, Mercy College, Dobbs Ferry, NY 10522, USA; Institute for Cell Biology and Neuroscience (CONICET-UBA), Buenos Aires, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Brusés
authors.affiliation: Institut des Neurosciences, INSERM U1051, 80 rue Augustin Fliche, 34091 Montpellier, France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Raoul
authors.affiliation: Institut des Neurosciences, INSERM U1051, 80 rue Augustin Fliche, 34091 Montpellier, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Scamps
authors.affiliation: IBMM, CNRS UMR 5247, Université de Montpellier, 1919 route de Mende, 34293 Montpellier, France. Electronic address: pierre.charnet@crbm.cnrs.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Charnet
mesh_terms: D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D018274:Electroporation; D008564:Membrane Potentials / Q000502:physiology; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology; D009865:Oocytes; D018408:Patch-Clamp Techniques; D013116:Spinal Cord / Q000502:physiology; D014982:Xenopus laevis; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D020864:Calcium Channels, N-Type; D002412:Cations; D001464:Barium; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins; D002118:Calcium
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)