Development and Function of the Voltage-Gated Sodium Current in Immature Mammalian Cochlear Inner Hair Cells

Inner hair cells (IHCs), the primary sensory receptors of the mammalian cochlea, fire spontaneous Ca(2+) action potentials before the onset of hearing. Although this firing activity is mainly sustained by a depolarizing L-type (Ca(V)1.3) Ca(2+) current (I (Ca)), IHCs also transiently express a large Na(+) current (I (Na)). We aimed to investigate the specific contribution of I (Na) to the action potentials, the nature of the channels carrying the current and whether the biophysical properties of I (Na) differ between low- and high-frequency IHCs. We show that I (Na) is highly temperature-dependent and activates at around −60 mV, close to the action potential threshold. Its size was larger in apical than in basal IHCs and between 5% and 20% should be available at around the resting membrane potential (−55 mV/−60 mV). However, in vivo the availability of I (Na) could potentially increase to >60% during inhibitory postsynaptic potential activity, which transiently hyperpolarize IHCs down to as far as −70 mV. When IHCs were held at −60 mV and I (Na) elicited using a simulated action potential as a voltage command, we found that I (Na) contributed to the subthreshold depolarization and upstroke of an action potential. We also found that I (Na) is likely to be carried by the TTX-sensitive channel subunits Na(V)1.1 and Na(V)1.6 in both apical and basal IHCs. The results provide insight into how the biophysical properties of I (Na) in mammalian cochlear IHCs could contribute to the spontaneous physiological activity during cochlear maturation in vivo.