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.
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.
Chabbert
Christian
C
INSERM U583, UM2 cc089, place E. Bataillon, 34095 Montpellier cedex 5, France.
Mechaly
Ilana
I
Sieso
Victor
V
Giraud
Pierre
P
Brugeaud
Aurore
A
Lehouelleur
Jacques
J
Couraud
François
F
Valmier
Jean
J
Sans
Alain
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D017931:DNA Primers; D004558:Electric Stimulation; D004594:Electrophysiology; D004622:Embryo, Mammalian / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects*; D007150:Immunohistochemistry; D015640:Ion Channel Gating / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012444:Saccule and Utricle / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000235:genetics; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin