Triggered Calcium Lightning Programs Cochlear Development

ABSTRACT Spontaneous calcium (Ca 2+ ) waves play a critical role as internal stimuli in the early developing auditory system before the onset of sensory experiences. However, neither the spatiotemporal control of spontaneous Ca 2+ waves nor their impacts on auditory development are well understood. Here we report that a lateral array of inner supporting cells (ISCs) beneath the inner hair cells displays a spontaneous ultra‐long, ultra‐fast, transient Ca 2+ flash, termed “Ca 2+ lightning”, which triggers a series of simultaneous bursts of Ca 2+ waves in the whole cochlea, before the ear canal opening. The Ca 2+ lightning margins the cochlear ISCs at different developmental stages that correspondingly exhibit different Ca 2+ activities. Triggered by an ATP‐induced high‐level Ca 2+ wave, the Ca 2+ lightning rapidly propagates laterally into neighboring ISCs through the intricate interplay of the T‐type Ca 2+ channel, Anoctamin 1 (Ano1) Ca 2+ ‐activated Cl − channel and Connexin 26 (Cx26). The genetic deletion of Cav3.2, Ano1, or Cx26 abrogates Ca 2+ lightning flashes and dysregulates cell development and functions in peripheral cochleae. We propose that cochlear Ca 2+ lightning flashes orderly with Ca 2+ waves together orchestrate the spatiotemporal maturation processes of the peripheral auditory system before the onset of hearing.