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J Biol Chem
2014 Feb 21;2898:4735-42. doi: 10.1074/jbc.M113.535898.
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Conopeptide Vt3.1 preferentially inhibits BK potassium channels containing β4 subunits via electrostatic interactions.
Li M
,
Chang S
,
Yang L
,
Shi J
,
McFarland K
,
Yang X
,
Moller A
,
Wang C
,
Zou X
,
Chi C
,
Cui J
.
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BK channel β subunits (β1-β4) modulate the function of channels formed by slo1 subunits to produce tissue-specific phenotypes. The molecular mechanism of how the homologous β subunits differentially alter BK channel functions and the role of different BK channel functions in various physiologic processes remain unclear. By studying channels expressed in Xenopus laevis oocytes, we show a novel disulfide-cross-linked dimer conopeptide, Vt3.1 that preferentially inhibits BK channels containing the β4 subunit, which is most abundantly expressed in brain and important for neuronal functions. Vt3.1 inhibits the currents by a maximum of 71%, shifts the G-V relation by 45 mV approximately half-saturation concentrations, and alters both open and closed time of single channel activities, indicating that the toxin alters voltage dependence of the channel. Vt3.1 contains basic residues and inhibits voltage-dependent activation by electrostatic interactions with acidic residues in the extracellular loops of the slo1 and β4 subunits. These results suggest a large interaction surface between the slo1 subunit of BK channels and the β4 subunit, providing structural insight into the molecular interactions between slo1 and β4 subunits. The results also suggest that Vt3.1 is an excellent tool for studying β subunit modulation of BK channels and for understanding the physiological roles of BK channels in neurophysiology.
Bowersox,
Pharmacotherapeutic potential of omega-conotoxin MVIIA (SNX-111), an N-type neuronal calcium channel blocker found in the venom of Conus magus.
1998, Pubmed
Bowersox,
Pharmacotherapeutic potential of omega-conotoxin MVIIA (SNX-111), an N-type neuronal calcium channel blocker found in the venom of Conus magus.
1998,
Pubmed
Brayden,
Regulation of arterial tone by activation of calcium-dependent potassium channels.
1992,
Pubmed
Brenner,
Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4.
2000,
Pubmed
Brenner,
BK channel beta4 subunit reduces dentate gyrus excitability and protects against temporal lobe seizures.
2005,
Pubmed
Butler,
mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels.
1993,
Pubmed
,
Xenbase
Contreras,
Modulation of BK channel voltage gating by different auxiliary β subunits.
2012,
Pubmed
,
Xenbase
Cui,
Molecular mechanisms of BK channel activation.
2009,
Pubmed
Deng,
FMRP regulates neurotransmitter release and synaptic information transmission by modulating action potential duration via BK channels.
2013,
Pubmed
Du,
Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder.
2005,
Pubmed
,
Xenbase
Dworetzky,
Phenotypic alteration of a human BK (hSlo) channel by hSlobeta subunit coexpression: changes in blocker sensitivity, activation/relaxation and inactivation kinetics, and protein kinase A modulation.
1996,
Pubmed
Fan,
A novel conotoxin from Conus betulinus, kappa-BtX, unique in cysteine pattern and in function as a specific BK channel modulator.
2003,
Pubmed
Galvez,
Purification and characterization of a unique, potent, peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus.
1990,
Pubmed
Garcia-Valdes,
Slotoxin, alphaKTx1.11, a new scorpion peptide blocker of MaxiK channels that differentiates between alpha and alpha+beta (beta1 or beta4) complexes.
2001,
Pubmed
Giangiacomo,
Mechanism of iberiotoxin block of the large-conductance calcium-activated potassium channel from bovine aortic smooth muscle.
1992,
Pubmed
Gruslova,
An extracellular domain of the accessory β1 subunit is required for modulating BK channel voltage sensor and gate.
2012,
Pubmed
Gu,
BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells.
2007,
Pubmed
Hanner,
The beta subunit of the high-conductance calcium-activated potassium channel contributes to the high-affinity receptor for charybdotoxin.
1997,
Pubmed
Kanjhan,
Tertiapin-Q blocks recombinant and native large conductance K+ channels in a use-dependent manner.
2005,
Pubmed
,
Xenbase
Lancaster,
Properties of two calcium-activated hyperpolarizations in rat hippocampal neurones.
1987,
Pubmed
Lee,
{beta} subunit-specific modulations of BK channel function by a mutation associated with epilepsy and dyskinesia.
2009,
Pubmed
,
Xenbase
Lewis,
Conus venom peptide pharmacology.
2012,
Pubmed
Liu,
Location of modulatory beta subunits in BK potassium channels.
2010,
Pubmed
Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed
MacKinnon,
Mechanism of charybdotoxin block of the high-conductance, Ca2+-activated K+ channel.
1988,
Pubmed
Maupetit,
PEP-FOLD: an online resource for de novo peptide structure prediction.
2009,
Pubmed
McManus,
Functional role of the beta subunit of high conductance calcium-activated potassium channels.
1995,
Pubmed
,
Xenbase
Meera,
A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin.
2000,
Pubmed
,
Xenbase
Meera,
Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus.
1997,
Pubmed
Meredith,
BK calcium-activated potassium channels regulate circadian behavioral rhythms and pacemaker output.
2006,
Pubmed
Miljanich,
Ziconotide: neuronal calcium channel blocker for treating severe chronic pain.
2004,
Pubmed
Miller,
Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle.
,
Pubmed
Olivera,
Conus peptides: biodiversity-based discovery and exogenomics.
2006,
Pubmed
Phillips,
Scalable molecular dynamics with NAMD.
2005,
Pubmed
Robitaille,
Presynaptic calcium signals and transmitter release are modulated by calcium-activated potassium channels.
1992,
Pubmed
Shi,
Mechanism of magnesium activation of calcium-activated potassium channels.
2002,
Pubmed
Shi,
Inhibition of martentoxin on neuronal BK channel subtype (alpha+beta4): implications for a novel interaction model.
2008,
Pubmed
Tao,
Enhancement effects of martentoxin on glioma BK channel and BK channel (α+β1) subtypes.
2011,
Pubmed
Terlau,
Conus venoms: a rich source of novel ion channel-targeted peptides.
2004,
Pubmed
Vanommeslaeghe,
CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields.
2010,
Pubmed
Wallner,
Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a transmembrane beta-subunit homolog.
1999,
Pubmed
,
Xenbase
Wang,
Blocking effect and crystal structure of natrin toxin, a cysteine-rich secretory protein from Naja atra venom that targets the BKCa channel.
2005,
Pubmed
Weiger,
A novel nervous system beta subunit that downregulates human large conductance calcium-dependent potassium channels.
2000,
Pubmed
Windley,
A novel family of insect-selective peptide neurotoxins targeting insect large-conductance calcium-activated K+ channels isolated from the venom of the theraphosid spider Eucratoscelus constrictus.
2011,
Pubmed
Wu,
Novel conopeptides in a form of disulfide-crosslinked dimer.
2010,
Pubmed
Xia,
Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells.
1999,
Pubmed
,
Xenbase
Yang,
An epilepsy/dyskinesia-associated mutation enhances BK channel activation by potentiating Ca2+ sensing.
2010,
Pubmed
,
Xenbase
Yao,
BmP09, a "long chain" scorpion peptide blocker of BK channels.
2005,
Pubmed
,
Xenbase
Zeng,
Redox-sensitive extracellular gates formed by auxiliary beta subunits of calcium-activated potassium channels.
2003,
Pubmed
