Biomedical subjects

Sonja J Pyott

Publications and source records attributed to Sonja J Pyott.

3 recordsLinked to original sources

PubMed2006

Cochlear function in mice lacking the BK channel alpha, beta1, or beta4 subunits.

Large conductance voltage- and calcium-activated potassium (BK) channels are important for regulating many essential cellular functions, from neuronal action potential shape and firing rate to smooth muscle contractility. In amphibians, reptiles, and birds, BK channels mediate the intrinsic frequency tuning of the cochlear hair cell by an electrical resonance mechanism. In contrast, inner hair cells of the mammalian cochlea are extrinsically tuned by accessory structures of the cochlea. Nevertheless, BK channels are present in inner hair cells and encode a fast activating outward current. To understand the role of the BK channel alpha and beta subunits in mammalian inner hair cells, we analyzed the morphology, physiology, and function of these cells from mice lacking the BK channel alpha (Slo-/-) and also the beta1 and beta4 subunits (beta1/4-/-). Beta1/4-/- mice showed normal subcellular localization, developmental acquisition, and expression of BK channels. Beta1/4-/- mice showed normal cochlear function as indicated by normal auditory brainstem responses and distortion product otoacoustic emissions. Slo-/- mice also showed normal cochlear function despite the absence of the BKalpha subunit and the absence of fast activating outward current from the inner hair cells. Moreover, microarray analyses revealed no compensatory changes in transcripts encoding ion channels or transporters in the cochlea from Slo-/- mice. Slo-/- mice did, however, show increased resistance to noise-induced hearing loss. These findings reveal the fundamentally different contribution of BK channels to nonmammalian and mammalian hearing and suggest that BK channels should be considered a target in the prevention of noise-induced hearing loss.

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PubMed2004

Extrasynaptic localization of inactivating calcium-activated potassium channels in mouse inner hair cells.

Auditory hair cells from nonmammalian vertebrates are electrically tuned to specific sound frequencies primarily by the interactions of voltage-gated calcium channels and calcium-activated potassium (BK) channels colocalized at synaptic active zones. Mammalian inner hair cells are not electrically tuned and, yet, BK channels are also thought to reside at active zones. Using patch-clamp recordings and immunofluorescence, we characterized BK channel expression in mouse inner hair cells. Unexpectedly, these channels have inactivating currents and are clustered near the apex of the cell away from synaptic sites near the base. These results indicate a novel function of BK channels in mammalian inner hair cells and provide a framework for future research.

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PubMed2002

The effects of temperature on vesicular supply and release in autaptic cultures of rat and mouse hippocampal neurons.

Membrane fusion plays a central role in the synaptic vesicle cycle. While many of the pre- and postfusion events have been investigated at room temperature, few researchers have investigated these processes at more physiologically relevant temperatures. We have used autaptic cultures of hippocampal neurons to investigate changes in the size and refilling rate of the readily releasable pool (RRP) of synaptic vesicles brought about by an increase in temperature from 25 to 35 degrees C. We have also examined temperature-dependent changes in spontaneous and action potential (AP)-evoked release as well as the fraction of the RRP that is released during an AP. Although we found a threefold increase in the refilling rate of the RRP at the higher temperature, there was no apparent change in the size of the RRP with increased temperature. Moreover, we observed a slight but significant decrease in the quanta released during an AP. This increased refilling rate and decreased release probability resulted in a reduction of both the degree and time course of synaptic depression during high frequency stimulation at the higher temperature. This reduction in synaptic depression was accompanied by an increased maintenance of the synchronous component of release during high frequency stimulation. These findings indicate that the dynamics of vesicular supply and release in hippocampal neurons at room temperature are significantly different at near physiological temperatures and could affect our present understanding of the way in which individual neurons and networks of neurons process information.

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