Consequences of the Stoichiometry ofSlo1α and Auxiliary β Subunits on Functional Properties of Large-Conductance Ca2+-Activated K+Channels

Wang, Yingwei; Ding, Jiu; Xia, Xiaoming; Lingle, Christopher J.

doi:10.1523/jneurosci.22-05-01550.2002

Cited by 122 publications

(158 citation statements)

References 33 publications

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“…Rates of trypsin removal of inactivation were fit with the following function (Ding et al, 1998;Wang et al, 2002):…”

Section: Methodsmentioning

confidence: 99%

“…This function postulates that a single ID is sufficient for inactivation, but that n domains per channel must be cleaved by trypsin to remove inactivation (Ding et al, 1998;Wang et al, 2002). Empirically optimal fits to recovery time courses among different patches and datasets were obtained with n of ϳ1.8 -3.0.…”

Section: Methodsmentioning

confidence: 99%

“…The rates for onset and recovery from inactivation are based on previous information about the inactivation rates and steady-state open probability of ␣ ϩ ␤2 channels (Xia et al, 1999;Wang et al, 2002;Benzinger et al, 2006), for which the P o for ␣ ϩ ␤2 channels at 10 M Ca 2ϩ is ϳ0.05 at Ϫ80 mV, ϳ0.8 at 0 mV, and Ͼ0.95 at ϩ60 mV (Xia et al, 1999). We assume that intrinsic inactivation rate, k i , is negligibly voltage dependent, being ϳ12.5 s Ϫ1 (Xia et al, 1999;Wang et al, 2002). Steady-state inactivation data at 10 M Ca 2ϩ suggest that the probability of being inactivated (P i ) is ϳ0.2 at Ϫ80 mV and ϳ0.98 at 0 mV .…”

Section: Modeling Of the Trypsin-mediated Removal Of Inactivationmentioning

confidence: 99%

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A Limited Access Compartment between the Pore Domain and Cytosolic Domain of the BK Channel

Zhang¹,

Zhong²,

Ding³

et al. 2006

J. Neurosci.

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Cytosolic N-terminal segments of many K ϩ channel subunits mediate rapid blockade of ion permeation by physical occlusion of the ion-conducting pore. For some channels with large cytosolic structures, access to the channel pore by inactivation domains may occur through lateral entry pathways or "side portals" that separate the pore domain and associated cytosolic structures covering the axis of the permeation pathway. However, the extent to which side portals control access of molecules to the channel or influence channel gating is unknown. Here we use removal of inactivation by trypsin as a tool to examine basic residue accessibility in both the N terminus of the native auxiliary ␤2 subunit of Ca 2ϩ -activated, BK-type K ϩ channels and ␤2 subunits with artificial inactivating N termini. The results show that, for BK channels, side portals define a protected space that precedes the channel permeation pathway and excludes small proteins such as trypsin but allows inactivation domains to enter. When channels are closed, inactivation domains readily pass through side portals, with a central antechamber preceding the permeation pathway occupied by an inactivation domain approximately half of the time under resting conditions. The restricted volume of the pathway through side portals is likely to influence kinetic properties of inactivation mechanisms, blockade by large pharmacological probes, and accessibility of modulatory factors to surfaces of the channel within the protected space.

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“…Rates of trypsin removal of inactivation were fit with the following function (Ding et al, 1998;Wang et al, 2002):…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Modeling Of the Trypsin-mediated Removal Of Inactivationmentioning

confidence: 99%

See 1 more Smart Citation

A Limited Access Compartment between the Pore Domain and Cytosolic Domain of the BK Channel

Zhang¹,

Zhong²,

Ding³

et al. 2006

J. Neurosci.

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“…Up to four β subunits may be associated with a tetrameric Slo1 channel (7,14). Each β subunit likely positions itself between two neighboring voltage-sensor domains of the Slo1 channel so that the extracellular side of TM1 is adjacent to S1 and S2 of one poreforming Slo1 subunit and that the extracellular end of TM2 is close to S0 of another Slo1 subunit (15)(16)(17).…”

mentioning

confidence: 99%

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

Hoshi

Tian

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Large-conductance Ca 2+ -and voltage-activated K + (BK) channels are well known for their functional versatility, which is bestowed in part by their rich modulatory repertoire. We recently showed that long-chain omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) found in oily fish lower blood pressure by activating vascular BK channels made of Slo1+β1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+β4 channels were just as well activated by DHA as vascular Slo1+β1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+β2, Slo1+LRRC26 (γ1), and Slo1 channels without auxiliary subunits. Mutagenesis of β1, β2, and β4 showed that the large effect of DHA in Slo1+β1 and Slo1+β4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the β1 and β4 subunits. Transfer of this amino acid pair from β1 or β4 to β2 introduces a large response to DHA in Slo1+β2. The presence of a pair of oppositely charged residues at the aforementioned positions in β subunits is associated with a large response to DHA. The Slo1 auxiliary subunits are expressed in a highly tissue-dependent fashion. Thus, the subunit composition-dependent stimulation by DHA demonstrates that BK channels are effectors of omega-3 fatty acids with marked tissue specificity.K Ca 1.1 | fish oil | lipids

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“…They are negative feedback regulators of cellular excitability and of [Ca 2ϩ ] i . BK channels are a complex of four ␣-subunits (1) and four ␤-subunits (2)(3)(4)(5)(6)(7). In addition to the S1-S6 transmembrane (TM) helices conserved in all voltage-gated K ϩ channels, ␣ contains a unique seventh TM helix, S0, N-terminal to S1-S6; furthermore, the first 19 residues preceding S0 are extracellular (Fig.…”

mentioning

confidence: 99%

Locations of the β1 transmembrane helices in the BK potassium channel

Liu¹,

Zakharov²,

Yang³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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BK channels are composed of ␣-subunits, which form a voltageand Ca 2؉ -gated potassium channel, and of modulatory ␤-subunits. The ␤1-subunit is expressed in smooth muscle, where it renders the BK channel sensitive to [Ca 2؉ ]i in a voltage range near the smoothmuscle resting potential and slows activation and deactivation. BK channel acts thereby as a damped feedback regulator of voltagedependent Ca 2؉ channels and of smooth muscle tone. We explored the contacts between ␣ and ␤1 by determining the extent of endogenous disulfide bond formation between cysteines substituted just extracellular to the two ␤1 transmembrane (TM) helices, TM1 and TM2, and to the seven ␣ TM helices, consisting of S1-S6, conserved in all voltage-dependent potassium channels, and the unique S0 helix, which we previously concluded was partly surrounded by S1-S4. We now find that the extracellular ends of ␤1 TM2 and ␣ S0 are in contact and that ␤1 TM1 is close to both S1 and S2. The extracellular ends of TM1 and TM2 are not close to S3-S6. In almost all cases, cross-linking of TM2 to S0 or of TM1 to S1 or S2 shifted the conductance-voltage curves toward more positive potentials, slowed activation, and speeded deactivation, and in general favored the closed state. TM1 and TM2 are in position to contribute, in concert with the extracellular loop and the intracellular N-and C-terminal tails of ␤1, to the modulation of BK channel function.auxiliary subunit ͉ cysteine substitution ͉ disulfide cross-linking ͉ electrophysiology ͉ mslo1 B K potassium channels have large conductances and are uniquely both voltage-and Ca 2ϩ -activated. They are negative feedback regulators of cellular excitability and of [Ca 2ϩ ] i . BK channels are a complex of four ␣-subunits (1) and four ␤-subunits (2-7). In addition to the S1-S6 transmembrane (TM) helices conserved in all voltage-gated K ϩ channels, ␣ contains a unique seventh TM helix, S0, N-terminal to S1-S6; furthermore, the first 19 residues preceding S0 are extracellular (Fig. 1A) (8).A large cytoplasmic domain, C-terminal to S6, contains two RCK domains, resembling those of the bacterial Ca 2ϩ -gated K ϩ channel, MthK (9). The voltage-sensitivity of the BK channel is a property of the membrane domain of ␣, whereas the Ca 2ϩ -sensitivity is conferred by the C-terminal cytoplasmic domain (10).The channel formed by BK ␣ is modulated by ␤-subunits. There are four types of ␤-subunits, ␤1, ␤2, ␤3, and ␤4, 191-235 residues in length (2-6). ␤-Subunits have short cytoplasmic Nand C-terminal segments, two TM helices, TM1 and TM2, and a large extracellular loop between them (Fig. 1B). The ␤1-subunit is expressed in smooth muscle. In the presence of Ca 2ϩ , it shifts the V 50 for channel activation toward the resting potential, around which channel opening becomes a roughly linear function of [Ca 2ϩ ] i in the physiologically relevant 1-10 M range. In addition, ␤1 slows both activation and deactivation. Activation of BK channels shifts the membrane potential to more negative values, suppressing the activity of L-ty...

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Consequences of the Stoichiometry ofSlo1α and Auxiliary β Subunits on Functional Properties of Large-Conductance Ca²⁺-Activated K⁺Channels

Cited by 122 publications

References 33 publications

A Limited Access Compartment between the Pore Domain and Cytosolic Domain of the BK Channel

A Limited Access Compartment between the Pore Domain and Cytosolic Domain of the BK Channel

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

Locations of the β1 transmembrane helices in the BK potassium channel

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