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G‐protein‐coupled receptor (GPCR) regulation of acid‐sensing ion channel 1a
Author(s) -
Staruschenko Alexander,
Stockand James D
Publication year - 2007
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.21.6.a1405-a
Subject(s) - g protein coupled receptor , ion channel , microbiology and biotechnology , acid sensing ion channel , receptor , chemistry , agonist , biophysics , biology , neuroscience , biochemistry
Acid‐sensing ion channels (ASIC) are neuronal Na + channels in the epithelial Na + channel/degenerin superfamily. 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. Neurotransmitters and modulators control neuronal excitability and function by ultimately influencing activity of membrane ion channels often through G‐protein‐coupled receptor signaling. Little is understood about cellular mechanisms controlling ASIC activity. Thus, we investigated possible regulation of ASIC1a by GPCR. We demonstrate here that both muscarinic (M1) and somatostatin (ST1) receptors modulate recombinant ASIC1a activity in CHO cells. The muscarinic agonist oxotremorine M applied to the bath strongly inhibited acid‐sensitive macroscopic ASIC1a currents in voltage‐clamped cells coexpressing the M1 receptor. Similarly, somatostatin inhibited the acid‐induced current in cells coexpressing ASIC1a and the ST1 receptor. These effects were fast, persistent and reversible. This is the first evidence that we are aware of, demonstrating GPCR regulation of ASIC. Such regulation may play a role in establishing and dynamically changing neuronal excitability. Supported by NIH, AHA and NKF.