SLO-2, a K+ channel with an unusual Cl− dependence

Yuan, Alex; Dourado, Michelle; Butler, Alice; Walton, N.; Wei, Aguan; Salkoff, Lawrence

doi:10.1038/77670

Cited by 109 publications

(124 citation statements)

References 40 publications

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“…In addition to the Ca 2ϩ -regulated Slo1 (Adelman et al, 1992;Butler et al, 1993) and the pH-regulated Slo3 (Schreiber et al, 1998), two additional homologs have been identified, Slo2.1 (Bhattacharjee et al, 2003), also termed Slick, and Slo2.2 (Joiner et al, 1998;Yuan et al, 2000Yuan et al, , 2003, also termed Slack. Slo2.2 subunits are regulated by both Na ϩ and Cl Ϫ (Yuan et al, 2003) and perhaps by Ca 2ϩ (Yuan et al, 2000), and Slo2.1 subunits, although less well characterized, also share sensitivity to Na ϩ and Cl Ϫ (Bhattacharjee et al, 2003). Thus, the hallmark of the Slo family of channels appears to be regulation by distinct cytosolic ligands.…”

Section: Discussionmentioning

confidence: 99%

Ligand-Dependent Activation of Slo Family Channels Is Defined by Interchangeable Cytosolic Domains

Xia¹,

Zhang²,

Lingle³

2004

J. Neurosci.

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Section: Discussionmentioning

confidence: 99%

Ligand-Dependent Activation of Slo Family Channels Is Defined by Interchangeable Cytosolic Domains

Xia¹,

Zhang²,

Lingle³

2004

J. Neurosci.

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“…1a. Two BK-like channels with somewhat smaller conductance than BK channels (100-200 pS) had either two conserved negative charges (mSlo3) (40,41) or one conserved negative charge (cSlo2) (42). MthK, a bacterial Ca 2ϩ -regulated K ϩ channel (31) with conductance of Ϸ100 pS at ϩ25 mV has two negative charges and one positive charge in the region equivalent to 321 and 324 of BK channels.…”

Section: Bk Channels Have a Ring Of Eight Negative Chargesmentioning

confidence: 99%

A ring of eight conserved negatively charged amino acids doubles the conductance of BK channels and prevents inward rectification

Brelidze

Niu

Magleby

2003

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

127

195

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Large-conductance Ca 2؉ -voltage-activated K ؉ channels (BK channels) control many key physiological processes, such as neurotransmitter release and muscle contraction. A signature feature of BK channels is that they have the largest single channel conductance of all K ؉ channels. Here we examine the mechanism of this large conductance. Comparison of the sequence of BK channels to lower-conductance K ؉ channels and to a crystallized bacterial K ؉ channel (MthK) revealed that BK channels have a ring of eight negatively charged glutamate residues at the entrance to the intracellular vestibule. This ring of charge, which is absent in lower-conductance K ؉ channels, is shown to double the conductance of BK channels for outward currents by increasing the concentration of K ؉ in the vestibule through an electrostatic mechanism. Removing the ring of charge converts BK channels to inwardly rectifying channels. Thus, a simple electrostatic mechanism contributes to the large conductance of BK channels.L arge-conductance Ca 2ϩ -voltage-activated K ϩ (BK) channels are activated in a highly synergistic manner by intracellular Ca 2ϩ (Ca i 2ϩ ) and membrane depolarization (1)(2)(3)(4)(5)(6)(7)(8)(9). When open, the efflux of K ϩ out of the cell hyperpolarizes the membrane potential, turning off voltage-dependent Ca 2ϩ channels and reducing the influx of Ca 2ϩ available to both activate BK channels and control cellular processes. This negative feedback mechanism allows BK channels to play a key role in regulating many physiological processes, such as neurotransmitter release (10, 11), repetitive firing of neurons (12), spike broadening during repetitive firing (13), the electrical tuning of hair cells in the cochlea (14,15), and muscle contraction (16).BK channels (for big K ϩ ) have the largest single-channel conductance of all K ϩ selective channels, being 250-300 pS in symmetrical 150 mM KCl (8,[17][18][19][20]. Like most K ϩ channels of lower conductance, BK channels have a tetrameric structure, with four ␣ subunits forming functional channels. BK channels also have the same selectivity filter sequence (GYG) found in most other K ϩ channels of lower conductance (21). Thus, the question arises as to why the conductance of BK channels is so big.Previous experimental and theoretical work has suggested that charged residues located in the vestibules and pores of ion channels can play a major role in controlling the unitary conductance through an electrostatic mechanism (22-30). Such rings of fixed charge could increase the concentration of the permeating ions in the vestibules of the channels, leading to increased availability of ions to transit the selectivity filter, which would increase the unitary (single-channel) conductance.In this study we show by comparison of the sequence of BK channels to lower-conductance K ϩ channels and to a bacterial K ϩ channel (MthK) crystallized in the open state (31) that BK channels have a ring of eight negatively charged glutamate residues at the entrance to the intracellular vestibule that ...

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“…The gene coding for BK was called Slowpoke or Slo and, after the cloning and expression of Slo2 (Yuan et al, 2000;Yuan et al, 2003) and Slo3 (Schreiber et al, 1998), was renamed Slo1. In the case of Kv channels, the channelforming protein possesses six transmembrane domains (S1-S6) containing the pore-forming domain S5-P-S6 and an S4 voltage-sensing element.…”

Section: Sensing Elementsmentioning

confidence: 99%

Large conductance Ca2+-activated K+ (BK) channel: Activation by Ca2+ and voltage

2006

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Large conductance Ca 2+ -activated K + (BK) channels belong to the S4 superfamily of K + channels that include voltage-dependent K + (Kv) channels characterized by having six (S1-S6) transmembrane domains and a positively charged S4 domain. As Kv channels, BK channels contain a S4 domain, but they have an extra (S0) transmembrane domain that leads to an external NH 2 -terminus. The BK channel is activated by internal Ca 2+ , and using chimeric channels and mutagenesis, three distinct Ca 2+ -dependent regulatory mechanisms with different divalent cation selectivity have been identified in its large COOH-terminus. Two of these putative Ca 2+ -binding domains activate the BK channel when cytoplasmic Ca 2+ reaches micromolar concentrations, and a low Ca 2+ affinity mechanism may be involved in the physiological regulation by Mg 2+ . The presence in the BK channel of multiple Ca 2+ -binding sites explains the huge Ca 2+ concentration range (0.1 μM-100 μM) in which the divalent cation influences channel gating. BK channels are also voltage-dependent, and all the experimental evidence points toward the S4 domain as the domain in charge of sensing the voltage. Calcium can open BK channels when all the voltage sensors are in their resting configuration, and voltage is able to activate channels in the complete absence of Ca 2+ . Therefore, Ca 2+ and voltage act independently to enhance channel opening, and this behavior can be explained using a two-tiered allosteric gating mechanism.

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SLO-2, a K+ channel with an unusual Cl− dependence

Cited by 109 publications

References 40 publications

Ligand-Dependent Activation of Slo Family Channels Is Defined by Interchangeable Cytosolic Domains

Ligand-Dependent Activation of Slo Family Channels Is Defined by Interchangeable Cytosolic Domains

A ring of eight conserved negatively charged amino acids doubles the conductance of BK channels and prevents inward rectification

Large conductance Ca2+-activated K+ (BK) channel: Activation by Ca2+ and voltage

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