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A transiently expressed SK current sustains and modulates action potential activity in immature mouse inner hair cells

journal contribution
posted on 2023-06-08, 06:22 authored by Walter Marcotti, Stuart L Johnson, Corne Kros
From just after birth, mouse inner hair cells (IHCs) expressed a Ca2+-activated K+ current that was reduced by intracellular BAPTA at concentrations = 1 mM. The block of this current by nifedipine suggests the direct involvement of Cav1.3 Ca2+ channels in its activation. On the basis of its high sensitivity to apamin (KD 360 pM) it was identified as a small-conductance Ca2+-activated K+ current (SK), probably SK2. A similar current was also found in outer hair cells (OHCs) from the beginning of the second postnatal week. In both cell types the appearance of the SK current coincided with their becoming responsive to acetylcholine (ACh), the main efferent neurotransmitter in the cochlea. The effect of ACh on IHCs was abolished when they were simultaneously superfused with strychnine, consistent with the presence of nicotinic ACh receptors (nAChRs). Extracellular Ca2+ either potentiated or blocked the nAChR current depending on its concentration, as previously reported for the recombinant a9a10 nAChR. Outward currents activated by ACh were reduced by blocking the SK current with apamin or by preventing SK current activation with intracellular BAPTA (= 10 mM). The endogenous mobile Ca2+ buffer concentration was estimated to be equivalent to about 1 mM BAPTA, suggesting that in physiological conditions the SK channel is significantly activated by Ca2+ influx through both Cav1.3 Ca2+ channels and a9a10 nAChRs. Current clamp experiments showed that in IHCs the SK current is required for sustaining a train of action potentials and also modulates their frequency when activated by ACh.


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Journal of Physiology







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