Characterization of acid-sensing ion channels in medium spiny neurons of mouse striatum.
Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. They are highly expressed in the striatum, where medium spiny neurons (MSNs) are a major population. Given that the properties of ASICs in MSNs are unknown, in this study, we characterized ASICs in MSNs of the mouse striatum. A rapid drop in extracellular pH induced transient inward currents in all MSNs. The pH value for half-maximal activation was 6.25, close to that obtained in homomeric ASIC1a channels. Based on psalmotoxin 1 and zinc sensitivity, ASIC1a (70.5% of neurons) and heteromeric ASIC1a-2 channels (29.5% of neurons) appeared responsible for the acid-induced currents in MSNs. ASIC currents were diminished in MSNs from ASIC1, but not ASIC2, null mice. Furthermore, a drop in pH induced calcium influx by activating homomeric ASIC1a channels. Activation of ASICs increased the membrane excitability of MSNs and lowering extracellular Ca2+ potentiated ASIC currents. Our data suggest that the homomeric ASIC1a channel represents a majority of the ASIC isoform in MSNs. The potential function of ASICs in the striatum requires further investigation.
Department of Basic Medical Science, University of Missouri-Kansas City School of Medicine, 2411 Holmes Street, Kansas City, MO 64108, USA.
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Jiang
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MH
Li
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CJ
Papasian
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D
Branigan
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Xiong
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JQ
Wang
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XP
Chu
D062565:Acid Sensing Ion Channels; D000200:Action Potentials / Q000502:physiology; D000584:Amiloride / Q000008:administration & dosage; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000008:administration & dosage; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010455:Peptides; D026941:Sodium Channel Blockers / Q000008:administration & dosage; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013111:Spider Venoms / Q000008:administration & dosage; D017967:Zinc Compounds / Q000008:administration & dosage
C568267:ASIC1 protein, mouse; C568265:ASIC2 protein, mouse; D062565:Acid Sensing Ion Channels; D002712:Chlorides; D009419:Nerve Tissue Proteins; C413209:PcTX1 protein, Psalmopoeus cambridgei; D010455:Peptides; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013111:Spider Venoms; D017967:Zinc Compounds; D000584:Amiloride; C016837:zinc chloride; D002118:Calcium