Intercellular Ca²⁺ signalling in the adult mouse cochlea

Abstract

Key points Intercellular Ca2+ waves are increases in cytoplasmic Ca2+ levels that propagate between cells.Periodic Ca2+ waves have been linked to gene regulation and are thought to play a crucial role in the development of our hearing epithelium, the organ of Corti and the acquisition of hearing.We observed regular periodic intercellular Ca2+ waves in supporting cells of an ex vivo preparation of the adult mouse organ of Corti, and these waves were found to propagate independently of extracellular ATP and were inhibited by the gap junction blockers 1‐octanol and carbenoxolone.Our results establish that the existence of periodic Ca2+ waves in the organ of Corti is not restricted to the prehearing period. AbstractWe have investigated wave‐like cytoplasmic calcium (Ca2+) signalling in an ex vivo preparation of the adult mouse organ of Corti. Two types of intercellular Ca2+ waves that differ in propagation distance and speed were observed. One type was observed to travel up to 100 μm with an average velocity of 7 μm/s. Such waves were initiated by local tissue damage in the outer hair cell region. The propagation distance was decreased when the purinergic receptor antagonists pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulfonic acid (PPADS; 50 μm) or suramin (150 μm) were added to the extracellular buffer. Immunocytochemical analysis and experiments with calcium indicator dyes showed that both P2X and P2Y receptors were present in supporting cells. A second class of waves identified to travel longitudinally along the organ of Corti propagated at a lower velocity of 1–3 μm/s. These ‘slow’ Ca2+ waves were particularly evident in the inner sulcus and Deiters’ cells. They travelled for distances of up to 500 μm. The slow Ca2+ signalling varied periodically (approximately one wave every 10 min) and was maintained for more than 3 h. The slow waves were not affected by apyrase, or by the P2 receptor agonists suramin (150 μm) or PPADS (50 μm) but were blocked by the connexin channel blockers octanol (1 mm) and carbenoxolone (100 μm). It is proposed that the observed Ca2+ waves might be a physiological response to a change in extracellular environment and may be involved in critical gene regulation activities in the supporting cells of the cochlea.

Acoustic Trauma Increases Ribbon Number and Size in Outer Hair Cells of the Mouse Cochlea

“…The model presented assumes that OHCs retain normal sensitivity. Also, it is known that acute tissue damage initiates spreading waves of activity among supporting cells via the release of ATP (Sirko et al 2019 ). Type II afferents are excited by ATP (Liu et al 2015 ), and could become sensitized in the presence of ATP as is observed in somatic nociceptors (Kress and Guenther 1999 ; Tominaga et al 2001 ).…”

Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space

“…Consistent with these observations, P2rx2 KO mice and humans with a P2RX2 variant (c.178G > T) experience progressive sensorineural hearing loss ( Yan et al, 2013 ). Ca 2+ imaging and recordings from adult cochleae have also revealed robust responses to UTP in the inner sulcus, pillar cells, and Dieters’ cells ( Sirko et al, 2019 ; Zhu and Zhao, 2010 ), suggesting that metabotropic purinergic receptors continue to be expressed. Following traumatic noise damage, ATP release could activate K + buffering mechanisms in supporting cells, enhance K + redistribution, reduce IHC depolarization and prevent excitotoxic damage.…”

Purinergic Signaling and Cochlear Injury-Targeting the Immune System?

“…The propagation of waves may involve two mechanisms: (a) ATP release via hemichannels and activation of ionotropic (i.e., P2X2 and/or P2X4) and metabotropic (i.e., P2Y2) purinergic receptors of neighbouring cells resulted in a faster wave and (b) IP 3 flow through gap junctions releasing internal Ca 2+ stores of the neighbouring cells is resulted in a slower wave [43,67,106,109,110,111,112,113,114]. More recently, this phenomenon was also observed in adult mouse organ of Corti [115]. These waves may function as early detectors of cochlear injury, but may also be involved in physiological mechanisms, for instance K + recycling through the supporting cells.…”