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The Journal of Neuroscience, May 15, 2000, 20(10):3563-3570

A Novel Nervous System  Subunit that Downregulates Human Large Conductance Calcium-Dependent Potassium Channels

Thomas M. Weiger^{1, 3}, Mats H. Holmqvist¹, Irwin B. Levitan¹, Frederick T. Clark², Scott Sprague², Wann-Jeng Huang², Pei Ge², Chichung Wang², Deborah Lawson², Mark E. Jurman², M. Alexandra Glucksmann², Inmaculada Silos-Santiago², Peter S. DiStefano², and Rory Curtis²

¹ Department of Biochemistry and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454, ² Millennium Pharmaceuticals, Cambridge, Massachusetts 02139, and ³ Department of Molecular Neurobiology and Cell Physiology, Institute of Zoology, University of Salzburg, A-5020 Salzburg, Austria

The pore-forming  subunits of many ion channels are associated with auxiliary subunits that influence channel expression, targeting, and function. Several different auxiliary () subunits for large conductance calcium-dependent potassium channels of the Slowpoke family have been reported, but none of these  subunits is expressed extensively in the nervous system. We describe here the cloning and functional characterization of a novel Slowpoke 4 auxiliary subunit in human and mouse, which exhibits only limited sequence homology with other  subunits. This 4 subunit coimmunoprecipitates with human and mouse Slowpoke. 4 is expressed highly in human and monkey brain in a pattern that overlaps strikingly with Slowpoke  subunit, but in contrast to other Slowpoke  subunits, it is expressed little (if at all) outside the nervous system. Also in contrast to other  subunits, 4 downregulates Slowpoke channel activity by shifting its activation range to more depolarized voltages and slowing its activation kinetics. 4 may be important for the critical roles played by Slowpoke channels in the regulation of neuronal excitability and neurotransmitter release.

Key words: potassium channel; subunit; in situ hybridization; Slowpoke; maxi K; calcium-dependent potassium channel

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20103563-08$05.00/0

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