title: Neurotrophin-4 modulates the mechanotransducer Cav3.2 T-type calcium current in mice down-hair neurons.
abstract: The T-type Ca2+ channel Cav3.2 is expressed in nociceptive and mechanosensitive sensory neurons. The mechanosensitive D-hair (down-hair) neurons, which innervate hair follicles, are characterized by a large-amplitude Cav3.2 T-current involved in the amplification of slow-moving stimuli. The molecules and signalling pathways that regulate T-current expression in mechanoreceptors are unknown. In the present study, we investigated the effects of NT-4 (neurotrophin-4) on Cav3.2 T-current expression in D-hair neurons in vitro. Interruption of the supply of NT-4 with peripheral nerve axotomy induced a non-transcriptional decrease in the T-current amplitude of fluorogold-labelled axotomized sensory neurons. The T-current amplitude was restored by incubation with NT-4. Deletion of NT-4 through genetic ablation resulted in a similar selective loss of the large-amplitude T-current in NT-4-/- sensory neurons, which was rescued by the addition of NT-4. NT-4 had no effect on the T-current in Cav3.2-/- D-hair neurons. Neither the biophysical properties of the T-current nor the transcript expression of Cav3.2 were modified by NT-4. Pharmacological screening of signalling pathways activated under the high-affinity NT-4 receptor TrkB (tropomyosin receptor kinase B) identified a role for PI3K (phosphoinositide 3-kinase) in the potentiation of T-current. The results of the present study demonstrate the post-transcriptional up-regulation of the Cav3.2 T-current through TrkB activation and identify NT-4 as a target-derived factor that regulates the mechanosensitive function of D-hair neurons through expression of the T-current.
authors: Inserm U-1051, Montpellier, F34000, France.
authors: Cécile
authors: C
authors: Hilaire
authors: Olivier
authors: O
authors: Lucas
authors: Jean
authors: J
authors: Valmier
authors: Frédérique
authors: F
authors: Scamps
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006197:Hair; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*
chemical_list: C504883:Cacna1h protein, mouse; D020747:Calcium Channels, T-Type; D009414:Nerve Growth Factors; C073922:neurotrophin 4; D002118:Calcium