Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a.
Chen, Xuanmao; Grunder, Stefan
[Miscellaneous Article] Journal of Physiology. 579(3):657-670, March 15, 2007.

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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.

Copyright (C) 2007 Blackwell Publishing Ltd.