科研之友
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摘要
Cholinergic neurons of the brainstem olivary complex project to and inhibit outer hair cells (OHCs), refining acoustic sensitivity of the mammalian cochlea. In all vertebrate hair cells studied to date, cholinergic inhibition results from the combined action of ionotropic acetylcholine receptors and associated calcium-activated potassium channels. Although inhibition was thought to involve exclusively small conductance (SK potassium channels), recent findings have shown that BK channels also contribute to inhibition in basal, high-frequency OHCs after the onset of hearing. Here we show that the waveform of randomly timed IPSCs (evoked by high extracellular potassium) in high-frequency OHCs is altered by blockade of either SK or BK channels, with BK channels supporting faster synaptic waveforms and SK channels supporting slower synaptic waveforms. Consistent with these findings, IPSCs recorded from high-frequency OHCs that express BK channels are briefer than IPSCs recorded from low-frequency (apical) OHCs that do not express BK channels and from immature high-frequency OHCs before the developmental onset of BK channel expression. Likewise, OHCs of BK alpha(-/-) mice lacking the pore-forming alpha-subunit of BK channels have longer IPSCs than do the OHCs of BK alpha(+/+) littermates. Furthermore, serial reconstruction of electron micrographs showed that postsynaptic cisterns of BK alpha(-/-) OHCs were smaller than those of BK alpha(+/+) OHCs, and immunofluorescent quantification showed that efferent presynaptic terminals of BK alpha(-/-) OHCs were smaller than those of BK alpha(+/+) OHCs. Together, these findings indicate that BK channels contribute to postsynaptic function, and influence the structural maturation of efferent-OHC synapses.
- 出版日期2015-2-4
