Development and regeneration of hair cells share common functional features

Abstract

The structural phenotype of neural connections in the auditory brainstem is sculpted by spontaneous and stimulus-induced neural activities during development. However, functional and molecular mechanisms of spontaneous action potentials (SAPs) in the developing cochlea are unknown. Additionally, it is unclear how regenerating hair cells establish their neural ranking in the constellation of neurons in the brainstem. We have demonstrated that a transient Ca 2؉ current produced by the Cav3.1 channel is expressed early in development to initiate spontaneous Ca 2؉ spikes. Ca 2ϩ currents ͉ cochlea ͉ hearing ͉ spontaneous activity

Molecular Identity and Functional Properties of a Novel T-Type Ca2+ Channel Cloned From the Sensory Epithelia of the Mouse Inner Ear

“…The correlation between the expression of Ca v 3.1 and the propensity of nonsensory cells to proliferate (Holley 2005) is also remarkable and it is conceivable that the Ca v 3.1 channels in cells in the inner ear may be an index for cell division. Indeed, a recent report has demonstrated the presence of a T-type current in developing hair cells (Levic et al 2007), which is consistent with the hypothesis that Ca v 3.1 may be important for cellular differentiation. Also important, the robust expression of Ca v 3.1 and reappearance in regenerating hair cells is in further agreement with the concept that expression of T-type currents begets cellular development.…”

“…The kinetic phenotype of the inner ear Ca v 3.1 channels in heterologous expression system, with respect to the fast inactivation, was distinct from typical Ca 2ϩ currents recorded from developing hair cells (Levic et al 2007). Moreover, the results were not surprising since recapitulation of the native cell current properties invariably requires auxiliary subunits (Dolphin et al 1999;Lacerda et al 1994;Leuranguer et al 1998).…”

“…Ca 2ϩ influx from T-type Ca 2ϩ currents gives rise to many scenarios for developing and regenerating hair cells (Levic et al 2007). Membrane excitability is promoted when the low-threshold features of the current amplify the depolarizing inputs.…”

Plasticity in Membrane Cholesterol Contributes toward Electrical Maturation of Hearing

“…Basilar papillae were isolated as described previously (4). All experiments were performed within 5-45 min of isolation.…”

“…To achieve the post-hearing phenotype, pre-hearing hair cells undergo a precise and conserved transition from spontaneous action potentials (SAPs) 2 to graded generator potentials (2,3). The importance of SAPs in the developing auditory system for synaptic refinement is reflected in the recapitulation of the preserved process in regenerating hair cells (4). Moreover, the electrical transition to graded receptor potential, which occurs at embryonic day (E) 18 in the chick and postnatal day (P) 12 in the mouse, coincides perfectly well with increased hearing sensitivity (3,(5)(6)(7)(8).…”