Spontaneous calcium (Ca2+) 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 Ca2+ 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 Ca2+ flash, termed "Ca2+ lightning", which triggers a series of simultaneous bursts of Ca2+ waves in the whole cochlea, before the ear canal opening. The Ca2+ lightning margins the cochlear ISCs at different developmental stages that correspondingly exhibit different Ca2+ activities. Triggered by an ATP-induced high-level Ca2+ wave, the Ca2+ lightning rapidly propagates laterally into neighboring ISCs through the intricate interplay of the T-type Ca2+ channel, Anoctamin 1 (Ano1) Ca2+-activated Cl- channel and Connexin 26 (Cx26). The genetic deletion of Cav3.2, Ano1, or Cx26 abrogates Ca2+ lightning flashes and dysregulates cell development and functions in peripheral cochleae. We propose that cochlear Ca2+ lightning flashes orderly with Ca2+ waves together orchestrate the spatiotemporal maturation processes of the peripheral auditory system before the onset of hearing.
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