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© The Rockefeller University Press, 0022-1295/1997//301/ $5.00
Journal of General Physiology, Volume 109, Number 3, 1997


Article

Transfer of Voltage Independence from a Rat Olfactory Channel to the Drosophila Ether-à-go-go K+ Channel

Chih-Yung Tang and Diane M. Papazian

From the Department of Physiology, School of Medicine, and Molecular Biology Institute, University of California, Los Angeles, California 90095-1751

The S4 segment is an important part of the voltage sensor in voltage-gated ion channels. Cyclic nucleotide-gated channels, which are members of the superfamily of voltage-gated channels, have little inherent sensitivity to voltage despite the presence of an S4 segment. We made chimeras between a voltage-independent rat olfactory channel (rolf) and the voltage-dependent ether-à-go-go K+ channel (eag) to determine the basis of their divergent gating properties. We found that the rolf S4 segment can support a voltage-dependent mechanism of activation in eag, suggesting that rolf has a potentially functional voltage sensor that is silent during gating. In addition, we found that the S3-S4 loop of rolf increases the relative stability of the open conformation of eag, effectively converting eag into a voltage-independent channel. A single charged residue in the loop makes a significant contribution to the relative stabilization of the open state in eag. Our data suggest that cyclic nucleotide-gated channels such as rolf contain a voltage sensor which, in the physiological voltage range, is stabilized in an activated conformation that is permissive for pore opening.

Key Words: cyclic nucleotide-gated channel • voltage-gated channel • voltage dependence • potassium channel • patch clamp


Address correspondence to Diane M. Papazian, Ph.D., Department of Physiology, UCLA School of Medicine, Box 951751, Los Angeles, CA 90095-1751. Fax: 310-206-5661; E-mail: papazian{at}physiology.medsch.ucla.edu


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