BK channels are linked to inositol 1,4,5-triphosphate receptors via lipid rafts: a novel mechanism for coupling [Ca(2+)](i) to ion channel activation.

BK channels are linked to inositol 1,4,5-triphosphate receptors via lipid rafts: a novel mechanism for coupling [Ca(2+)](i) to ion channel activation. Research Abstract Details 

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BK channels are linked to inositol 1,4,5-triphosphate receptors via lipid rafts: a novel mechanism for coupling [Ca(2+)](i) to ion channel activation. Abstract Text:

Amy K Weaver,Michelle L Olsen,Michael B McFerrin,Harald Sontheimer,Amy K Weaver,Michelle L Olsen,Michael B McFerrin,Harald Sontheimer,Amy K Weaver,Michelle L Olsen,Michael B McFerrin,Harald Sontheimer,

Glioma cells prominently express a unique splice variant of a large conductance, calcium-activated potassium channel (BK channel). These channels transduce changes in intracellular calcium to changes of K(+) conductance in the cells and have been implicated in growth control of normal and malignant cells. The Ca(2+) increase that facilitates channel activation is thought to occur via activation of intracellular calcium release pathways or influx of calcium through Ca(2+)-permeable ion channels. We show here that BK channel activation involves the activation of inositol 1,4,5-triphosphate receptors (IP(3)R), which localize near BK channels in specialized membrane domains called lipid rafts. Disruption of lipid rafts with methyl-beta-cyclodextrin disrupts the functional association of BK channel and calcium source resulting in a >50% reduction in K(+) conductance mediated by BK channels. The reduction of BK current by lipid raft disruption was overcome by the global elevation of intracellular calcium through inclusion of 750 nm Ca(2+) in the pipette solution, indicating that neither the calcium sensitivity of the channel nor their overall number was altered. Additionally, pretreatment of glioma cells with 2-aminoethoxydiphenyl borate to inhibit IP(3)Rs negated the effect of methyl-beta-cyclodextrin, providing further support that IP(3)Rs are the calcium source for BK channels. Taken together, these data suggest a privileged association of BK channels in lipid raft domains and provide evidence for a novel coupling of these Ca(2+)-sensitive channels to their second messenger source.

BK channels are linked to inositol 1,4,5-triphosphate receptors via lipid rafts: a novel mechanism for coupling [Ca(2+)](i) to ion channel activation. Publishing Authors By Initials

AK Weaver,ML Olsen,MB McFerrin,H Sontheimer,AK Weaver,ML Olsen,MB McFerrin,H Sontheimer,AK Weaver,ML Olsen,MB McFerrin,H Sontheimer,

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BK channels are linked to inositol 1,4,5-triphosphate receptors via lipid rafts: a novel mechanism for coupling [Ca(2+)](i) to ion channel activation. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 31558-68

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 21

MONTH: 08

YEAR: 2007

BK channels are linked to inositol 1,4,5-triphosphate receptors via lipid rafts: a novel mechanism for coupling [Ca(2+)](i) to ion channel activation. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

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Grant and Affiliation Information for BK channels are linked to inositol 1,4,5-triphosphate receptors via lipid rafts: a novel mechanism for coupling [Ca(2+)](i) to ion channel activation.

AFFILIATION: Department of Neurobiology, Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Country: United States

AGENCY: United States NINDS

GRANT: R01-NS36692

ACRONYM: NS

MEDLINETA: J Biol Chem

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