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Developmental change in the electrophysiological and pharmacological properties of acid‐sensing ion channels in CNS neurons
Author(s) -
Li Minghua,
Kratzer Eric,
Inoue Koichi,
Simon Roger P.,
Xiong ZhiGang
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.192922
Subject(s) - acid sensing ion channel , ion channel , electrophysiology , neuroscience , biology , desensitization (medicine) , patch clamp , biophysics , chemistry , microbiology and biotechnology , biochemistry , receptor
Acid‐sensing ion channels (ASICs) are proton‐gated cation channels that play important roles in the CNS including synaptic plasticity and acidosis‐mediated neuronal injury. ASIC1a and ASIC2a subunits are predominant in CNS neurons, where homomultimeric and heteromultimeric channel configurations co‐exist. Since ASIC1a and ASIC2a have dramatic differences in pH sensitivity, Ca 2+ permeability and channel kinetics, any change in the level of individual subunits may have significant effects on the properties and functions of ASICs. Using patch‐clamp recording, fluorescent Ca 2+ imaging and molecular biological techniques, we show dramatic developmental changes in the properties of ASICs in mouse cortical neurons. For example, the amplitude of ASIC currents increases whereas desensitization decreases with neuronal maturation. Decreased H + affinity and acid‐evoked [Ca 2+ ] i but increased Zn 2+ potentiation were also recorded in mature neurons. RT‐PCR revealed significant increases in the ratio of ASIC2/ASIC1 mRNA with neuronal maturation. Thus, contributions of ASIC1a and ASIC2a to overall ASIC‐mediated responses undergo distinct developmental changes. These findings may help in understanding the precise role of ASICs in physiological and pathological conditions at different developmental stages.