| First Author | Eckrich T | Year | 2018 |
| Journal | Front Mol Neurosci | Volume | 11 |
| Pages | 264 | PubMed ID | 30104958 |
| Mgi Jnum | J:310672 | Mgi Id | MGI:6763680 |
| Doi | 10.3389/fnmol.2018.00264 | Citation | Eckrich T, et al. (2018) Fast Ca(2+) Transients of Inner Hair Cells Arise Coupled and Uncoupled to Ca(2+) Waves of Inner Supporting Cells in the Developing Mouse Cochlea. Front Mol Neurosci 11:264 |
| abstractText | Before the onset of hearing, which occurs around postnatal day 12 (P12) in mice, inner hair cells (IHCs) of the immature cochlea generate sound-independent Ca(2+) action potentials (APs), which stimulate the auditory pathway and guide maturation of neuronal circuits. During these early postnatal days, intercellular propagating Ca(2+) waves elicited by ATP-induced ATP release are found in inner supporting cells (ISCs). It is debated whether IHCs are able to fire Ca(2+) APs independently or require a trigger by an ISC Ca(2+) wave. To identify the Ca(2+) transients of IHCs underlying Ca(2+) APs and to analyze their dependence on ISC Ca(2+) waves, we performed fast Ca(2+) imaging of Fluo-8 AM-loaded organs of Corti at P4/P5. Fast Ca(2+) transients (fCaTs) generated by IHCs were simultaneously imaged with Ca(2+) waves in ISCs. ISC Ca(2+) waves frequently evoked bursts consisting of >5 fCaTs in multiple adjacent IHCs. Although Ca(2+) elevations of small amplitude appeared to be triggered by ISC Ca(2+) waves in IHCs of Cav1.3 knockout mice we never observed fCaTs, indicating their requirement for Ca(2+) influx through Cav1.3 channels. The Ca(2+) wave-triggered Ca(2+) upstroke in wildtype IHCs occurred 0.52 +/- 0.27 s later than the rise of the Ca(2+) signal in the adjacent ISCs. In comparison, superfusion of 1 muM ATP elicited bursts of fCaTs in IHCs starting 0.99 +/- 0.34 s prior to Ca(2+) elevations in adjacent ISCs. PPADS irreversibly abolished Ca(2+) waves in ISCs and reversibly reduced fCaTs in IHCs indicating differential involvement of P2 receptors. IHC and ISC Ca(2+) signals were however unaltered in P2X2R/P2X3R double knockout or in P2X7R knockout mice. Together, our data revealed a fairly similar occurrence of fCaTs within a burst (56.5%) compared with 43.5% as isolated single fCaTs or in groups of 2-5 fCaTs (minibursts). We provide evidence that IHCs autonomously generate single fCaTs and minibursts whereas bursts synchronized between neighboring IHCs were mostly triggered by ISC Ca(2+) waves. Neonatal IHCs thus spontaneously generate electrical and Ca(2+) activity, which is enhanced and largely synchronized by activity of ISCs of Kolliker's organ indicating two sources of spontaneous activity in the developing auditory system. |
