ATP-induced morphological changes in supporting cells of the developing cochlea

Abstract

The developing cochlea of mammals contains a large group of columnar-shaped cells, which together form a structure known as Kölliker's organ. Prior to the onset of hearing, these inner supporting cells periodically release adenosine 5′-triphosphate (ATP), which activates purinergic receptors in surrounding supporting cells, inner hair cells and the dendrites of primary auditory neurons. Recent studies indicate that purinergic signaling between inner supporting cells and inner hair cells initiates bursts of action potentials in auditory nerve fibers before the onset of hearing. ATP also induces prominent effects in inner supporting cells, including an increase in membrane conductance, a rise in intracellular Ca 2+ , and dramatic changes in cell shape, although the importance of ATP signaling in non-sensory cells of the developing cochlea remains unknown. Here, we review current knowledge pertaining to purinergic signaling in supporting cells of Kölliker's organ and focus on the mechanisms by which ATP induces changes in their morphology. We show that these changes in cell shape are preceded by increases in cytoplasmic Ca 2+ , and provide new evidence indicating that elevation of intracellular Ca 2+ and IP 3 are sufficient to initiate shape changes. In addition, we discuss the possibility that these ATP-mediated morphological changes reflect crenation following the activation of Ca 2+ -activated Cl − channels, and speculate about the possible functions of these changes in cell morphology for maturation of the cochlea.

Synaptic transmission between end bulbs of Held and bushy cells in the cochlear nucleus of mice with a mutation in Otoferlin

“…The similarities and differences between two groups of induced deafness and natural deafness mutations provide insights into how spontaneous activity in hair cells before the onset of hearing affects the cochlear nuclei (Johnson et al 2011(Johnson et al , 2013Kros et al 1998;Tritsch et al 2007Tritsch et al , 2010Tritsch and Bergles 2010). Mutations that prevent synaptic transmission from hair cells, including mutations in otoferlin (Pangrsic et al 2010;Roux et al 2006), vesicular glutamate transporter3 (Vglut3) (Seal et al 2008), and Ca v 1.3 (Platzer et al 2000), block activation of spiral ganglion cells by electrical activity both before and after the onset of hearing, whereas those that affect mechanotransduction, including mutations in espin in jerker mice and TMC in deafness mice (Kim et al 2013;Kurima et al 2002), affect activity after the onset of hearing but not before.…”

“…However, electrical activity occurs even before the onset of hearing in auditory circuits; that activity, especially in the second postnatal week, regulates synaptic transmission from hair cells (Beutner and Moser 2001;Johnson et al 2011Johnson et al , 2013Kros et al 1998). Before hearing begins, supporting cells in the cochlea induce action potentials in small groups of adjacent inner hair cells that in turn evoke periodic bursts of suprathreshold responses in the auditory nerve that are propagated to the cortex (Tritsch et al 2007(Tritsch et al , 2010Tritsch and Bergles 2010). Synaptotagmin IV contributes to shaping synaptic responses in adult inner hair cells and immature outer hair cells ), but after the third postnatal day (P3) synaptic transmission between inner hair cells and spiral ganglion neurons, the cells whose axons are auditory nerve fibers (ANFs), depends largely on the detection of calcium by Otoferlin (Beurg et al 2010;Roux et al 2006).…”

Purinergic signalling during development and ageing

“…A transient structure, Köllicker's organ, consisting of epithelial cells that lie adjacent to the hair cells, appears during the development of the cochlea. Spontaneous electrical potentials in these cells were mediated by spontaneous release of ATP via connexin hemichannels to act via P2X and P2Y receptors [251,252]. These cells exhibit spontaneous Ca 2+ waves activated by ATP [253] and may allow the establishment of the tonotopic organization of the cochlea and spiral ganglion cell innervation, although this is disputed [254].…”

Spontaneous activity in the developing auditory system

“…Similar events can be elicited by exogenous ATP or UTP, an agonist of P2Y receptors, and inhibited by purinergic receptor antagonists (suramin, PPADS). Strikingly, these cells shrink or crenate when stimulated with ATP or UTP, an effect that is triggered by a rise in intracellular Ca 2+ (Tritsch et al 2010b). Although the significance of these crenations is not known, it provides a mean to pinpoint the source of ATP -since all of the cells crenate when exposed to ATP, the site of crenation indicates where ATP was released.…”