HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/C682    most recent 00127.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Vukicevic, M. Articles by Kellenberger, S. Search for Related Content PubMed PubMed Citation Articles by Vukicevic, M. Articles by Kellenberger, S.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Modulatory effects of acid-sensing ion channels on action potential generation in hippocampal neurons

Department of Pharmacology and Toxicology, University of Lausanne, CH-1005 Lausanne, Switzerland

Submitted 5 March 2004 ; accepted in final form 23 April 2004

Extracellular acidification has been shown to generate action potentials (APs) in several types of neurons. In this study, we investigated the role of acid-sensing ion channels (ASICs) in acid-induced AP generation in brain neurons. ASICs are neuronal Na⁺ channels that belong to the epithelial Na⁺ channel/degenerin family and are transiently activated by a rapid drop in extracellular pH. We compared the pharmacological and biophysical properties of acid-induced AP generation with those of ASIC currents in cultured hippocampal neurons. Our results show that acid-induced AP generation in these neurons is essentially due to ASIC activation. We demonstrate for the first time that the probability of inducing APs correlates with current entry through ASICs. We also show that ASIC activation in combination with other excitatory stimuli can either facilitate AP generation or inhibit AP bursts, depending on the conditions. ASIC-mediated generation and modulation of APs can be induced by extracellular pH changes from 7.4 to slightly <7. Such local extracellular pH values may be reached by pH fluctuations due to normal neuronal activity. Furthermore, in the plasma membrane, ASICs are localized in close proximity to voltage-gated Na⁺ and K⁺ channels, providing the conditions necessary for the transduction of local pH changes into electrical signals.

cellular excitability; neuronal signaling; pH

This article has been cited by other articles:

				B. Duan, L.-J. Wu, Y.-Q. Yu, Y. Ding, L. Jing, L. Xu, J. Chen, and T.-L. Xu Upregulation of Acid-Sensing Ion Channel ASIC1a in Spinal Dorsal Horn Neurons Contributes to Inflammatory Pain Hypersensitivity J. Neurosci., October 10, 2007; 27(41): 11139 - 11148. [Abstract] [Full Text] [PDF]

				J.-H. Cho and C. C. Askwith Potentiation of acid-sensing ion channels by sulfhydryl compounds Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2161 - C2174. [Abstract] [Full Text] [PDF]

				X. Chen and S. Grunder Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a J. Physiol., March 15, 2007; 579(3): 657 - 670. [Abstract] [Full Text] [PDF]

				O. Poirot, T. Berta, I. Decosterd, and S. Kellenberger Distinct ASIC currents are expressed in rat putative nociceptors and are modulated by nerve injury J. Physiol., October 1, 2006; 576(1): 215 - 234. [Abstract] [Full Text] [PDF]

				F. Mercado, I. A. Lopez, D. Acuna, R. Vega, and E. Soto Acid-Sensing Ionic Channels in the Rat Vestibular Endorgans and Ganglia J Neurophysiol, September 1, 2006; 96(3): 1615 - 1624. [Abstract] [Full Text] [PDF]