A critical period of prehearing spontaneous Ca2+ spiking is required for hair‐bundle maintenance in inner hair cells

Sensory‐independent Ca²⁺ spiking regulates the development of mammalian sensory systems. In the immature cochlea, inner hair cells (IHCs) fire spontaneous Ca²⁺ action potentials (APs) that are generated either intrinsically or by intercellular Ca²⁺ waves in the nonsensory cells. The extent to which either or both of these Ca²⁺ signalling mechansims are required for IHC maturation is unknown. We find that intrinsic Ca²⁺ APs in IHCs, but not those elicited by Ca²⁺ waves, regulate the maturation and maintenance of the stereociliary hair bundles. Using a mouse model in which the potassium channel Kir2.1 is reversibly overexpressed in IHCs (Kir2.1‐OE), we find that IHC membrane hyperpolarization prevents IHCs from generating intrinsic Ca²⁺ APs but not APs induced by Ca²⁺ waves. Absence of intrinsic Ca²⁺ APs leads to the loss of mechanoelectrical transduction in IHCs prior to hearing onset due to progressive loss or fusion of stereocilia. RNA‐sequencing data show that pathways involved in morphogenesis, actin filament‐based processes, and Rho‐GTPase signaling are upregulated in Kir2.1‐OE mice. By manipulating in vivo expression of Kir2.1 channels, we identify a “critical time period” during which intrinsic Ca²⁺ APs in IHCs regulate hair‐bundle function.