A transiently expressed SK current sustains and modulates action potential activity in immature mouse inner hair cells.
From just after birth, mouse inner hair cells (IHCs) expressed a Ca(2+)-activated K(+) current that was reduced by intracellular BAPTA at concentrations >or= 1 mM. The block of this current by nifedipine suggests the direct involvement of Ca(v)1.3 Ca(2+) channels in its activation. On the basis of its high sensitivity to apamin (K(D) 360 pM) it was identified as a small-conductance Ca(2+)-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 Ca(2+) either potentiated or blocked the nAChR current depending on its concentration, as previously reported for the recombinant alpha9alpha10 nAChR. Outward currents activated by ACh were reduced by blocking the SK current with apamin or by preventing SK current activation with intracellular BAPTA (>or= 10 mM). The endogenous mobile Ca(2+) buffer concentration was estimated to be equivalent to about 1 mM BAPTA, suggesting that in physiological conditions the SK channel is significantly activated by Ca(2+) influx through both Ca(v)1.3 Ca(2+) channels and alpha9alpha10 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.
School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK.
Walter
W
Marcotti
Stuart L
SL
Johnson
Corné J
CJ
Kros
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001030:Apamin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004622:Embryo, Mammalian; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D009925:Organ of Corti / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D051640:Small-Conductance Calcium-Activated Potassium Channels
C496898:Kcnn2 protein, mouse; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid