PMID- 12963806 OWN - NLM STAT- MEDLINE DCOM- 20040715 LR - 20181113 IS - 0022-3751 (Print) IS - 1469-7793 (Electronic) IS - 0022-3751 (Linking) VI - 553 IP - Pt 1 DP - 2003 Nov 15 TI - Voltage-gated Na+ channel activation induces both action potentials in utricular hair cells and brain-derived neurotrophic factor release in the rat utricle during a restricted period of development. PG - 113-23 AB - The mammalian utricular sensory receptors are commonly believed to be non-spiking cells with electrical activity limited to graded membrane potential changes. Here we provide evidence that during the first post-natal week, the sensory hair cells of the rat utricle express a tetrodotoxin (TTX)-sensitive voltage-gated Na+ current that displays most of the biophysical and pharmacological characteristics of neuronal Na+ current. Single-cell RT-PCR reveals that several alpha-subunit isoforms of the Na+ channels are co-expressed within a single hair cell, with a major expression of Nav1.2 and Nav1.6 subunits. In neonatal hair cells, 30 % of the Na+ channels are available for activation at the resting potential. Depolarizing current injections in the range of the transduction currents are able to trigger TTX-sensitive action potentials. We also provide evidence of a TTX-sensitive activity-dependent brain-derived neurotrophic factor (BDNF) release by early post-natal utricle explants. Developmental analysis shows that Na+ currents decrease dramatically from post-natal day 0 (P0) to P8 and become almost undetectable at P21. Concomitantly, depolarizing stimuli fail to induce both action potential and BDNF release at P20. The present findings reveal that vestibular hair cells express neuronal-like TTX-sensitive Na+ channels able to generate Na+-driven action potentials only during the early post-natal period of development. During the same period an activity-dependent BDNF secretion by utricular explants has been demonstrated. This could be an important mechanism involved in vestibular sensory system differentiation and synaptogenesis. FAU - Chabbert, Christian AU - Chabbert C AD - INSERM U583, UM2 cc089, place E. Bataillon, 34095 Montpellier cedex 5, France. FAU - Mechaly, Ilana AU - Mechaly I FAU - Sieso, Victor AU - Sieso V FAU - Giraud, Pierre AU - Giraud P FAU - Brugeaud, Aurore AU - Brugeaud A FAU - Lehouelleur, Jacques AU - Lehouelleur J FAU - Couraud, Francois AU - Couraud F FAU - Valmier, Jean AU - Valmier J FAU - Sans, Alain AU - Sans A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20030908 PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DNA Primers) RN - 0 (Sodium Channel Agonists) RN - 0 (Sodium Channel Blockers) RN - 0 (Sodium Channels) RN - 4368-28-9 (Tetrodotoxin) SB - IM MH - Action Potentials/drug effects MH - Animals MH - Animals, Newborn/physiology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - DNA Primers MH - Electric Stimulation MH - Electrophysiology MH - Embryo, Mammalian/physiology MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Hair Cells, Auditory, Inner/*drug effects MH - Immunohistochemistry MH - Ion Channel Gating/physiology MH - Membrane Potentials/drug effects/physiology MH - Patch-Clamp Techniques MH - Pregnancy MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction MH - Saccule and Utricle/*drug effects/growth & development/*metabolism MH - Signal Transduction/drug effects MH - *Sodium Channel Agonists MH - Sodium Channel Blockers/pharmacology MH - Sodium Channels/genetics MH - Synapses/drug effects/physiology MH - Tetrodotoxin/pharmacology PMC - PMC2343473 EDAT- 2003/09/10 05:00 MHDA- 2004/07/16 05:00 PMCR- 2004/11/15 CRDT- 2003/09/10 05:00 PHST- 2003/09/10 05:00 [pubmed] PHST- 2004/07/16 05:00 [medline] PHST- 2003/09/10 05:00 [entrez] PHST- 2004/11/15 00:00 [pmc-release] AID - jphysiol.2003.043034 [pii] AID - 10.1113/jphysiol.2003.043034 [doi] PST - ppublish SO - J Physiol. 2003 Nov 15;553(Pt 1):113-23. doi: 10.1113/jphysiol.2003.043034. Epub 2003 Sep 8.