Abstract
We recently reported that a histidine (H191) in the S3-S4 loop of domain I is critical for nickel inhibition of the Cav3.2 T-type Ca2+ channel. As in Cav3.2, two histidine residues are commonly found in the IS3-IS4 loops of mammalian Cav2.3 Ca2+ channels, which are also blocked by low micromolar concentrations of nickel. We show here by site-directed mutagenesis and electrophysiology that both residues contribute to the nickel sensitivity of Cav2.3, with H183 being more critical than H179. These findings strongly suggest that both H179 and H183 in the IS3-IS4 loop are essential structural determinants required for nickel sensitive inhibition of the Cav2.3.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Calcium Channels, R-Type / chemistry*
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Calcium Channels, R-Type / metabolism
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Cation Transport Proteins / antagonists & inhibitors*
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Cation Transport Proteins / chemistry*
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Cation Transport Proteins / metabolism
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Dose-Response Relationship, Drug
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Female
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Histidine / metabolism*
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Humans
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Ion Channel Gating / drug effects
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Molecular Sequence Data
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Mutant Proteins / chemistry
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Mutant Proteins / metabolism
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Nickel / pharmacology*
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Protein Structure, Secondary
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Sequence Alignment
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Structure-Activity Relationship
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Xenopus
Substances
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CACNA1E protein, human
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Calcium Channels, R-Type
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Cation Transport Proteins
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Mutant Proteins
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Histidine
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Nickel