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

doi:10.1113/jphysiol.2006.120733

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

Xuanmao Chen¹ and
Stefan Gründer¹

¹University of Würzburg, Department of Physiology II, 97070 Würzburg, Germany

Corresponding author S. Gründer: Department of Physiology II, Röntgenring 9, 97070 Würzburg, Germany. Email: stefan.gruender{at}mail.uni-wuerzburg.de

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.