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Acta Physiologica 2009; Volume 195, Supplement 669
The 88th Annual Meeting of The German Physiological Society
3/22/2009-3/25/2009
Giessen, Germany
CHARACTERIZATION OF SHARKASIC1B, AN ANCIENT FORM OF AN ACID-SENSING ION CHANNEL
Abstract number: P368
Springauf1 A., Grunder1 S.
1Department of Physiology, Uniklinik Aachen, Aachen
Acid-sensing ion channels (ASICs) are cation-permeable membrane proteins activated by extracellular H+. Four genes and six spliced forms have been identified to date. They belong to the large class of DEG/ENaC channels and share a common topology with cytosolic termini, two transmembrane domains and a large extracellular loop. So far, ASICs have been found only in vertebrates. Recently, an ASIC has been isolated from a low vertebrate, the shark Squalus acanthias, which shares a sequence identity of 66% with rat ASIC1. In addition to this high overall sequence identity, amino acids which are known to be important for proton-gating of ASICs are also conserved in the shark ASIC (sharkASIC1b). SharkASIC1b has been reported to be proton-insensitive, however.
Here we show that sharkASIC1b is proton-sensitive: similar to other ASICs, acidic solutions elicit a transient current in cells expressing sharkASIC1b; halfmaximal activation occurs at pH 6.6. Uncommon to most ASICs, the transient current is followed by a smaller persistent current. Furthermore and in contrast to the persistent current, the transient current shows no tachyphylaxis. Like other DEG/ENaC channels, shark ASIC1b can be blocked by amiloride with an IC50 of ~80 mM. Site directed mutagenesis reveals that a pair of highly conserved histidines (His101 and His102) that are crucial for proton-activation of ASICs also play a essential role in proton-activation of shark ASIC1b.
Taken together our results indicate that proton-sensitivity of ASICs arose early in vertebrate evolution. The unique characteristics of sharkASIC1b currents qualify this channel for a sensitive sensor of transient as well as sustained proton signals.
To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 195, Supplement 669 :P368