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ClC chloride channels play essential roles in membrane excitability and maintenance of osmotic balance. Despite the recent crystallization of two bacterial ClC-like proteins, the gating mechanism for these channels remains unclear. In this study we tested scorpion venom for the presence of novel peptide inhibitors of ClC channels, which might be useful tools for dissecting the mechanisms underlying ClC channel gating. Recently, it has been shown that a peptide component of venom from the scorpion L. quinquestriatus hebraeus inhibits the CFTR chloride channel from the intracellular side. Using two-electrode voltage clamp we studied the effect of scorpion venom on ClC-0, -1, and -2, and found both dose- and voltage-dependent inhibition only of ClC-2. Comparison of voltage-dependence of inhibition by venom to that of known pore blockers revealed opposite voltage dependencies, suggesting different mechanisms of inhibition. Kinetic data show that venom induced slower activation kinetics compared to pre-venom records, suggesting that the active component(s) of venom may function as a gating modifier at ClC-2. Trypsinization abolished the inhibitory activity of venom, suggesting that the component(s) of scorpion venom that inhibits ClC-2 is a peptide.
Adjadj,
Solution structure of Lqh-8/6, a toxin-like peptide from a scorpion venom--structural heterogeneity induced by proline cis/trans isomerization.
1997, Pubmed
Adjadj,
Solution structure of Lqh-8/6, a toxin-like peptide from a scorpion venom--structural heterogeneity induced by proline cis/trans isomerization.
1997,
Pubmed Aromataris,
Fast and slow gating of CLC-1: differential effects of 2-(4-chlorophenoxy) propionic acid and dominant negative mutations.
2001,
Pubmed Bauer,
Completely functional double-barreled chloride channel expressed from a single Torpedo cDNA.
1991,
Pubmed
,
Xenbase Chen,
Extracellular zinc ion inhibits ClC-0 chloride channels by facilitating slow gating.
1998,
Pubmed
,
Xenbase Cuppoletti,
ClC-2 Cl- channels in human lung epithelia: activation by arachidonic acid, amidation, and acid-activated omeprazole.
2001,
Pubmed DeBin,
Chloride channel inhibition by the venom of the scorpion Leiurus quinquestriatus.
1991,
Pubmed DeBin,
Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion.
1993,
Pubmed de Santiago,
Quantitative analysis of the voltage-dependent gating of mouse parotid ClC-2 chloride channel.
2005,
Pubmed Devuyst,
Chloride channels in the kidney: lessons learned from knockout animals.
2002,
Pubmed Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed Dutzler,
Gating the selectivity filter in ClC chloride channels.
2003,
Pubmed
,
Xenbase Dutzler,
X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity.
2002,
Pubmed Fahlke,
Pore-forming segments in voltage-gated chloride channels.
1997,
Pubmed Fuller,
Inhibition of CFTR channels by a peptide toxin of scorpion venom.
2004,
Pubmed
,
Xenbase Furukawa,
Characteristics of rabbit ClC-2 current expressed in Xenopus oocytes and its contribution to volume regulation.
1998,
Pubmed
,
Xenbase Gross,
Agitoxin footprinting the shaker potassium channel pore.
1996,
Pubmed
,
Xenbase Haug,
Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies.
2003,
Pubmed Jentsch,
Molecular structure and physiological function of chloride channels.
2002,
Pubmed Jordt,
Molecular dissection of gating in the ClC-2 chloride channel.
1997,
Pubmed
,
Xenbase Koch,
The skeletal muscle chloride channel in dominant and recessive human myotonia.
1992,
Pubmed Lee,
Interaction between extracellular Hanatoxin and the resting conformation of the voltage-sensor paddle in Kv channels.
2003,
Pubmed
,
Xenbase Lipecka,
Distribution of ClC-2 chloride channel in rat and human epithelial tissues.
2002,
Pubmed Li-Smerin,
Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels.
1998,
Pubmed
,
Xenbase Lloyd,
A common molecular basis for three inherited kidney stone diseases.
1996,
Pubmed
,
Xenbase Machaca,
Asymmetrical distribution of Ca-activated Cl channels in Xenopus oocytes.
1998,
Pubmed
,
Xenbase Maduke,
A decade of CLC chloride channels: structure, mechanism, and many unsettled questions.
2000,
Pubmed Maertens,
Chlorotoxin does not inhibit volume-regulated, calcium-activated and cyclic AMP-activated chloride channels.
2000,
Pubmed McCarty,
Identification of a region of strong discrimination in the pore of CFTR.
2001,
Pubmed
,
Xenbase McDonough,
Interactions among toxins that inhibit N-type and P-type calcium channels.
2002,
Pubmed McDonough,
Voltage-dependent inhibition of N- and P-type calcium channels by the peptide toxin omega-grammotoxin-SIA.
1997,
Pubmed Murray,
Gestational and tissue-specific regulation of C1C-2 chloride channel expression.
1996,
Pubmed Naranjo,
A strongly interacting pair of residues on the contact surface of charybdotoxin and a Shaker K+ channel.
1996,
Pubmed
,
Xenbase Niemeyer,
A conserved pore-lining glutamate as a voltage- and chloride-dependent gate in the ClC-2 chloride channel.
2003,
Pubmed Norton,
The cystine knot structure of ion channel toxins and related polypeptides.
1998,
Pubmed Pusch,
Chloride dependence of hyperpolarization-activated chloride channel gates.
1999,
Pubmed
,
Xenbase Pusch,
Pharmacological characterization of chloride channels belonging to the ClC family by the use of chiral clofibric acid derivatives.
2000,
Pubmed
,
Xenbase Pusch,
Mechanism of block of single protopores of the Torpedo chloride channel ClC-0 by 2-(p-chlorophenoxy)butyric acid (CPB).
2001,
Pubmed
,
Xenbase Qu,
Anion permeation in Ca(2+)-activated Cl(-) channels.
2000,
Pubmed
,
Xenbase Ruta,
Functional analysis of an archaebacterial voltage-dependent K+ channel.
2003,
Pubmed Sherry,
Localization of ClC-2 Cl- channels in rabbit gastric mucosa.
2001,
Pubmed Sidach,
Kurtoxin, a gating modifier of neuronal high- and low-threshold ca channels.
2002,
Pubmed Simon,
Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III.
1997,
Pubmed Steinmeyer,
Inactivation of muscle chloride channel by transposon insertion in myotonic mice.
1991,
Pubmed Stobrawa,
Disruption of ClC-3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampus.
2001,
Pubmed Swartz,
Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites.
1997,
Pubmed
,
Xenbase Swartz,
Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels.
1997,
Pubmed Zdebik,
Additional disruption of the ClC-2 Cl(-) channel does not exacerbate the cystic fibrosis phenotype of cystic fibrosis transmembrane conductance regulator mouse models.
2004,
Pubmed Zúñiga,
The voltage-dependent ClC-2 chloride channel has a dual gating mechanism.
2004,
Pubmed
