Mapping the BKCa Channel's “Ca2+ Bowl”

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Mapping the BKCa Channel's “Ca2+ Bowl”

There is controversy over whether Ca(2+) binds to the BK(Ca) channel's intracellular domain or its integral-membrane domain and over whether or not mutations that reduce the channel's Ca(2+) sensitivity act at the point of Ca(2+) coordination. One region in the intracellular domain that has been implicated in Ca(2+) sensing is the "Ca(2+) bowl". This region contains many acidic residues, and la...

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Measuring the Influence of the BKCa β1 Subunit on Ca2+ Binding to the BKCa Channel

The large-conductance Ca(2+)-activated potassium (BK(Ca)) channel of smooth muscle is unusually sensitive to Ca(2+) as compared with the BK(Ca) channels of brain and skeletal muscle. This is due to the tissue-specific expression of the BK(Ca) auxiliary subunit beta1, whose presence dramatically increases both the potency and efficacy of Ca(2+) in promoting channel opening. beta1 contains no Ca(...

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TRPV4 forms a novel Ca2+ signaling complex with ryanodine receptors and BKCa channels.

Vasodilatory factors produced by the endothelium are critical for the maintenance of normal blood pressure and flow. We hypothesized that endothelial signals are transduced to underlying vascular smooth muscle by vanilloid transient receptor potential (TRPV) channels. TRPV4 message was detected in RNA from cerebral artery smooth muscle cells. In patch-clamp experiments using freshly isolated ce...

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N-arachidonoyl glycine suppresses Na+/Ca2+ exchanger-mediated Ca2+ entry into endothelial cells and activates BKCa channels independently of GPCRs

BACKGROUND AND PURPOSE N-Arachidonoyl glycine (NAGly) is a lipoamino acid with vasorelaxant properties. We aimed to explore the mechanisms of NAGly's action on unstimulated and agonist-stimulated endothelial cells. EXPERIMENTAL APPROACH The effects of NAGly on endothelial electrical signalling were studied in combination with vascular reactivity. KEY RESULTS In EA.hy926 cells, the sustained...

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Elimination of the BKCa Channel's High-Affinity Ca2+ Sensitivity

We report here a combination of site-directed mutations that eliminate the high-affinity Ca(2+) response of the large-conductance Ca(2+)-activated K(+) channel (BK(Ca)), leaving only a low-affinity response blocked by high concentrations of Mg(2+). Mutations at two sites are required, the "Ca(2+) bowl," which has been implicated previously in Ca(2+) binding, and M513, at the end of the channel'...

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ژورنال

عنوان ژورنال: Journal of General Physiology

سال: 2004

ISSN: 1540-7748,0022-1295

DOI: 10.1085/jgp.200409052