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J Physiol. 2007 Mar 15;579(Pt 3):657-70. Epub 2007 Jan 4.

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

Author information

1
Department of Physiology II, Röntgenring 9, 97070 Würzburg, Germany.

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.

PMID:
17204502
PMCID:
PMC2151377
DOI:
10.1113/jphysiol.2006.120733
[Indexed for MEDLINE]
Free PMC Article

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