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 Ca2+ action potentials before the onset of hearing. Although this firing activity is mainly sustained by a depolarizing L-type (Ca(V)1.3) Ca2+ 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.