Abstract
The acid-sensing ion channels (ASICs) are a family of ion channels expressed throughout the mammalian nervous system. The principal activator of ASICs is extracellular protons, and ASICs have been demonstrated to play a significant role in many physiologic and pathophysiologic processes, including synaptic transmission, nociception, and fear. However, not all ASICs are proton-sensitive: ASIC2a is activated by acid, whereas its splice variant ASIC2b is not. We made a series of chimeric ASIC2 proteins, and using whole-cell electrophysiology we have identified the minimal region of the ASIC2a extracellular domain that is required for ASIC2 proton activation: the first 87 amino acids after transmembrane domain 1. We next examined the function of different domains within the ASIC2b N-terminus and identified a region proximal to the first transmembrane domain that confers tachyphylaxis upon ASIC2a. We have thus identified domains of ASIC2 that are crucial to channel function and may be important for the function of other members of the ASIC family.
Footnotes
- Received November 17, 2014.
- Accepted January 12, 2015.
L.-N.S. is a student in the Biotechnology and Biological Sciences Research Council Doctoral Training Programme [Grant BB/J014540/1] and a recipient of the David James Pharmacology Award. S.S. is supported by the Cambridge International and European Trust. E.St.J.S. was supported by the Isaac Newton Trust/Wellcome Trust Institutional Strategic Support Fund/University of Cambridge Joint Research Grants Scheme.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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