https://dx.doi.org/10.1113/jphysiol.2006.120733">
 

Title

Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a

Abstract

The homomeric acid-sensing ion channel 1a (ASIC1a) is a H+-activated ion channel with important physiological functions and pathophysiological impact in the central nervous system. Here we show that homomeric ASIC1a is distinguished from other ASICs by a reduced response to successive acid stimulations. Such a reduced response is called tachyphylaxis. We show that tachyphylaxis depends on H+ permeating through ASIC1a, that tachyphylaxis is attenuated by extracellular Ca2+, and that tachyphylaxis is probably linked to Ca2+ permeability of ASIC1a. Moreover, we provide evidence that tachyphylaxis is probably due to a long-lived inactive state of ASIC1a. A deeper understanding of ASIC1a tachyphylaxis may lead to pharmacological control of ASIC1a activity that could be of potential benefit for the treatment of stroke.

Publication Date

3-14-2007

Journal Title

Journal of Physiology

Publisher

Wiley

Digital Object Identifier (DOI)

https://dx.doi.org/10.1113/jphysiol.2006.120733

Document Type

Article

Rights

© 2007 The Physiological Society