Compartmentalization of antagonistic Ca signals in developing cochlear hair cells.

During a critical developmental period, cochlear inner hair cells (IHCs) exhibit sensory-independent activity, featuring action potentials in which Ca ions play a fundamental role in driving both spiking and glutamate release onto synapses with afferent auditory neurons. This spontaneous activity is controlled by a cholinergic input to the IHC, activating a specialized nicotinic receptor with high Ca permeability, and coupled to the activation of hyperpolarizing SK channels. The mechanisms underlying distinct excitatory and inhibitory Ca roles within a small, compact IHC are unknown. Making use of Ca imaging, afferent auditory bouton recordings, and electron microscopy, the present work shows that unusually high intracellular Ca buffering and "subsynaptic" cisterns provide efficient compartmentalization and tight control of cholinergic Ca signals. Thus, synaptic efferent Ca spillover and cross-talk are prevented, and the cholinergic input preserves its inhibitory signature to ensure normal development of the auditory system.