Regulation of the Gating of BKCa Channel by Lipid Bilayer Thickness

Yuan, Changxia; O’Connell, Robert J.; Jacob, Robert F.; Mason, R. Preston; Treistman, Steven N.

doi:10.1074/jbc.m607593200

Cited by 68 publications

(84 citation statements)

References 65 publications

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“…Another possibility is that cholesterol depletion makes the membrane thinner, thus reducing the free energy difference between the closed and open state of the channel. Indeed, bilayer thickness has been found to modulate BK Ca activity in vitro (39). Yet another possibility is that cholesterol binds to BK Ca channels.…”

Section: Discussionmentioning

confidence: 99%

Activity of BKCa Channel Is Modulated by Membrane Cholesterol Content and Association with Na+/K+-ATPase in Human Melanoma IGR39 Cells

Tajima

Itokazu

Korpi

et al. 2011

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Activity of BKCa Channel Is Modulated by Membrane Cholesterol Content and Association with Na+/K+-ATPase in Human Melanoma IGR39 Cells

Tajima

Itokazu

Korpi

et al. 2011

Journal of Biological Chemistry

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“…For proper comparisons with previous data obtained by us (17,20,21,25) and others (19,22,31), studies were conducted at room temperature (20 -25°C).…”

Section: ϫ2mentioning

confidence: 99%

Multiple Cholesterol Recognition/Interaction Amino Acid Consensus (CRAC) Motifs in Cytosolic C Tail of Slo1 Subunit Determine Cholesterol Sensitivity of Ca2+- and Voltage-gated K+ (BK) Channels

Singh

McMillan

Bukiya

et al. 2012

Journal of Biological Chemistry

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“…However, further full activation obtained in the same patch with 30 M DiBAC 4 (3) in the bath reveals a marked differential sidedness of action that is not achievable by simply translocating DiBAC 4 (3) molecules across the membrane. This sidedness of action also argues against nonspecific mechanisms for channel activation that help us to exclude micellization of DiBAC 4 (3) or alterations in the local environment of the channel, like membrane curvature, known to modify the activity of BK channels (35). Moreover, the effect of the dye from the intracellular side is not observed in sodium channels where their voltage and timedependent properties remain largely unaffected by 30 M DiBAC 4 (3) (Fig.…”

Section: Discussionmentioning

confidence: 97%

DiBAC₄(3) hits a “sweet spot” for the activation of arterial large-conductance Ca²⁺-activated potassium channels independently of the β₁-subunit

Scornik

Bucciero

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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R, Pérez GJ. DiBAC4(3) hits a "sweet spot" for the activation of arterial large-conductance Ca 2ϩ -activated potassium channels independently of the ␤1-subunit. Am J Physiol Heart Circ Physiol 304: H1471-H1482, 2013. First published March 29, 2013; doi:10.1152/ajpheart.00939.2012.-The voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)] has been reported as a novel large-conductance Ca 2ϩ -activated K ϩ (BK) channel activator with selectivity for its ␤1-or ␤ 4-subunits. In arterial smooth muscle, BK channels are formed by a pore-forming ␣-subunit and a smooth muscle-abundant regulatory ␤1-subunit. This tissue specificity has driven extensive pharmacological research aimed at regulating arterial tone. Using animals with a disruption of the gene for the ␤ 1-subunit, we explored the effects of DiBAC4(3) in native channels from arterial smooth muscle. We tested the hypothesis that, in native BK channels, activation by DiBAC 4(3) relies mostly on its ␣-subunit. We studied BK channels from wildtype and transgenic ␤1-knockout mice in excised patches. BK channels from brain arteries, with or without the ␤1-subunit, were similarly activated by DiBAC 4(3). In addition, we found that saturating concentrations of DiBAC4(3) (ϳ30 M) promote an unprecedented persistent activation of the channel that negatively shifts its voltage dependence by as much as Ϫ300 mV. This "sweet spot" for persistent activation is independent of Ca 2ϩ and/or the ␤1-4-subunits and is fully achieved when DiBAC 4(3) is applied to the intracellular side of the channel. Arterial BK channel response to DiBAC4(3) varies across species and/or vascular beds. DiBAC4(3) unique effects can reveal details of BK channel gating mechanisms and help in the rational design of BK channel activators. BK channels; arterial smooth muscle; DiBAC 4(3), KCNMA1; KCNMB1 LARGE-CONDUCTANCE Ca 2ϩ -activated K ϩ (BK) channels belong to the family of ion channels with six transmembrane domains per subunit (6TM) and can be activated by both membrane depolarization and increase in intracellular Ca 2ϩ (14,16). In smooth muscle as well as in several other tissues, BK channels are formed by two different types of subunits, termed ␣-and ␤-subunits. The ␣-subunit contains the poreforming region, whereas the auxiliary ␤-subunit has regulatory functions (15,21).The smooth muscle ␤ 1 -subunit has been shown to have a crucial role as a molecular tuner for vasoregulation (3,24). Downregulation of the ␤ 1 -subunit was shown to have a role in a model of acquired hypertension (1) as well as in a model of genetic hypertension (2). Conversely, a polymorphism of the ␤ 1 -subunit that promotes a gain of function of the BK channel is associated with a low prevalence of diastolic hypertension in humans (12). Along these lines, a gain of function of arterial BK channels was found in a model of hemorrhagic shock, associated with an increased expression of the ␤ 1 -subunit (36). Moreover, the ␤ 1 -subunit expression was found to be reduced in animal models of diabetes (17,1...

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Regulation of the Gating of BKCa Channel by Lipid Bilayer Thickness

Cited by 68 publications

References 65 publications

Activity of BKCa Channel Is Modulated by Membrane Cholesterol Content and Association with Na+/K+-ATPase in Human Melanoma IGR39 Cells

Activity of BKCa Channel Is Modulated by Membrane Cholesterol Content and Association with Na+/K+-ATPase in Human Melanoma IGR39 Cells

Multiple Cholesterol Recognition/Interaction Amino Acid Consensus (CRAC) Motifs in Cytosolic C Tail of Slo1 Subunit Determine Cholesterol Sensitivity of Ca2+- and Voltage-gated K+ (BK) Channels

DiBAC₄(3) hits a “sweet spot” for the activation of arterial large-conductance Ca²⁺-activated potassium channels independently of the β₁-subunit

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Regulation of the Gating of BKCa Channel by Lipid Bilayer Thickness

Cited by 68 publications

References 65 publications

Activity of BKCa Channel Is Modulated by Membrane Cholesterol Content and Association with Na+/K+-ATPase in Human Melanoma IGR39 Cells

Activity of BKCa Channel Is Modulated by Membrane Cholesterol Content and Association with Na+/K+-ATPase in Human Melanoma IGR39 Cells

Multiple Cholesterol Recognition/Interaction Amino Acid Consensus (CRAC) Motifs in Cytosolic C Tail of Slo1 Subunit Determine Cholesterol Sensitivity of Ca2+- and Voltage-gated K+ (BK) Channels

DiBAC4(3) hits a “sweet spot” for the activation of arterial large-conductance Ca2+-activated potassium channels independently of the β1-subunit

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DiBAC₄(3) hits a “sweet spot” for the activation of arterial large-conductance Ca²⁺-activated potassium channels independently of the β₁-subunit