This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Yanochko, G. M. Articles by Yool, A. J. Search for Related Content PubMed PubMed Citation Articles by Yanochko, G. M. Articles by Yool, A. J.

Block by Extracellular Divalent Cations of Drosophila Big Brain Channels Expressed in Xenopus Oocytes

Gina M. Yanochko ^* and Andrea J. Yool ^* 

^* Program in Pharmacology and Toxicology and Department of Pharmacology and Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona 85724

Correspondence: Address reprint requests to Andrea J. Yool, Dept. of Physiology, PO Box 245051, University of Arizona, Tucson, AZ 85724-5051. Tel.: 520-626-2198; Fax: 520-626-2383; E-mail: ayool{at}u.arizona.edu.

Drosophila Big Brain (BIB) is a transmembrane protein encoded by the neurogenic gene big brain (bib), which is important for early development of the fly nervous system. BIB expressed in Xenopus oocytes is a monovalent cation channel modulated by tyrosine kinase signaling. Results here demonstrate that the BIB conductance shows voltage- and dose-dependent block by extracellular divalent cations Ca²⁺ and Ba²⁺ but not by Mg²⁺ in wild-type channels. Site-directed mutagenesis of negatively charged glutamate (Glu²⁷⁴) and aspartate (Asp²⁵³) residues had no effect on divalent cation block. However, mutation of a conserved glutamate at position 71 (Glu⁷¹) in the first transmembrane domain (M1) altered channel properties. Mutation of Glu⁷¹ to Asp introduced a new sensitivity to block by extracellular Mg²⁺; substitutions with asparagine or glutamine decreased whole-cell conductance; and substitution with lysine compromised plasma membrane expression. Block by divalent cations is important in other ion channels for voltage-dependent function, enhanced signal resolution, and feedback regulation. Our data show that the wild-type BIB conductance is attenuated by external Ca²⁺, suggesting that endogenous divalent cation block might be relevant for enhancing signal resolution or voltage dependence for the native signaling process in neuronal cell fate determination.

This article has been cited by other articles:

				N. Kaufmann, J. C. Mathai, W. G. Hill, J. A. T. Dow, M. L. Zeidel, and J. L. Brodsky Developmental expression and biophysical characterization of a Drosophila melanogaster aquaporin Am J Physiol Cell Physiol, August 1, 2005; 289(2): C397 - C407. [Abstract] [Full Text] [PDF]