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J. Biol. Chem., Vol. 279, Issue 18, 18783-18791, April 30, 2004

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A Family of Acid-sensing Ion Channels from the Zebrafish

WIDESPREAD EXPRESSION IN THE CENTRAL NERVOUS SYSTEM SUGGESTS A CONSERVED ROLE IN NEURONAL COMMUNICATION^*

Martin Paukert, Samuel Sidi¶, Claire Russell||, Maria Siba, Stephen W. Wilson||**, Teresa Nicolson, and Stefan Gründer

From the Department of Physiology II and Max-Planck-Institute of Developmental Biology, 72076 Tübingen, Germany, and ^||Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom

Acid-sensing ion channels (ASICs) are excitatory receptors for extracellular H⁺. Proposed functions include synaptic transmission, peripheral perception of pain, and mechanosensation. Despite the physiological importance of these functions, the precise role of ASICs has not yet been established. In order to increase our understanding of the physiological role and basic structure-function relationships of ASICs, we report here the cloning of six new ASICs from the zebrafish (zASICs). zASICs possess the basic functional properties of mammalian ASICs: activation by extracellular H⁺, Na⁺ selectivity, and block by micromolar concentrations of amiloride. The zasic genes are broadly expressed in the central nervous system, whereas expression in the peripheral nervous system is scarce. This pattern suggests a predominant role for zASICs in neuronal communication. Our results suggest a conserved function for receptors of extracellular H⁺ in the central nervous system of vertebrates.

Received for publication, February 10, 2004

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AJ609615–AJ609620.

^* This work was supported by grants from the Deutsche Forschungsgemeinschaft (to T. N. and S. G.) and the Wellcome Trust and European Community (to S. W. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Present address: Ecole Normale Supérieure, Laboratoire de Biologie Moléculaire du Developpement, 46 rue d'Ulm, 75005 Paris, France.

^** A Wellcome Trust Senior Research Fellow.

Present address: Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, Portland, OR 97201.

To whom correspondence should be addressed: Dept. of Physiology II, Gmelinstr. 5, D-72076 Tübingen, Germany. Tel.: 49-7071-29-77357; Fax: 49-7071-29-5074; E-mail: stefan.gruender{at}uni-tuebingen.de.

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