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Differential effects of Cd 2+ and Ni 2+ on distinct acid‐sensing ion channel (ASIC) isoforms
Author(s) -
Staruschenko Alexander,
Dorofeeva Natalia A,
Bolshakov Konstantin V,
Stockand James D
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a325-b
Subject(s) - homomeric , acid sensing ion channel , ion channel , biophysics , chemistry , divalent , amiloride , sodium channel , extracellular , epithelial sodium channel , gene isoform , biochemistry , biology , sodium , protein subunit , receptor , organic chemistry , gene
Acid‐sensing ion channels (ASIC) are neuronal Na + channels in the epithelial Na + channel/degenerin family. ASICs are transiently activated by rapid decreases in extracellular pH and are thought to play important roles in sensory perception and neuronal transmission and excitability. We demonstrate here that the divalent cations Ni 2+ and Cd 2+ dose‐dependently inhibit ASIC currents in native interneurons and in CHO cells heterologously expressing these channels. The effects of Ni 2+ and Cd 2+ are non‐competitive, voltage‐independent, fast and reversible. Neither metal affected activation and desensitization kinetics but rather decreased the maximal response to low pH. Moreover, distinct ASIC isoforms were differentially inhibited by Ni 2+ and Cd 2+ . External application of Ni 2+ rapidly inhibited activation of currents mediated by homomeric ASIC1a and heteromeric ASIC1a/2a channels without affecting currents mediated by ASIC2a and ASIC3 homomeric channels and ASIC1a/3, 2a/3 and 1a/2a/3 heteromeric channels. In contrast, external Cd 2+ inhibited currents carried by ASIC2a and ASIC3 homomeric channels and by ASIC1a/2a, 1a/3, 2a/3 and 1a/2a/3 heteromeric channels. The acid‐sensitive current in freshly isolated rat interneurons was inhibited by both Ni 2+ and Cd 2+ , implying that these cells have a mixed population of acid‐sensing ion channels.