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The Journal of Neuroscience, July 1, 2000, 20(13):4890-4903

Rectification and Rapid Activation at Low Ca2+ of Ca2+-Activated, Voltage-Dependent BK Currents: Consequences of Rapid Inactivation by a Novel beta  Subunit

Xiao-Ming Xia, Jiu-Ping Ding, Xu-Hui Zeng, Kai-Lai Duan, and Christopher J. Lingle

Washington University School of Medicine, Departments of Anesthesiology, and Anatomy and Neurobiology, St. Louis, Missouri 63110

A family of accessory beta  subunits significantly contributes to the functional diversity of large-conductance, Ca2+- and voltage-dependent potassium (BK) channels in native cells. Here we describe the functional properties of one variant of the beta  subunit family, which confers properties on BK channels totally unlike any that have as yet been observed. Coexpression of this subunit (termed beta 3) with Slo alpha  subunits results in rectifying outward currents and, at more positive potentials, rapidly inactivating (~1 msec) currents. The underlying rapid inactivation process results in an increase in the apparent activation rate of macroscopic currents, which is coupled with a shift in the activation range of the currents at low Ca2+. As a consequence, the currents exhibit more rapid activation at low Ca2+ relative to any other BK channel subunit combinations that have been examined. In part because of the rapid inactivation process, single channel openings are exceedingly brief. Although variance analysis suggests a conductance in excess of 160 pS, fully resolved single channel openings are not observed. The inactivation process results from a cytosolic N-terminal domain of the beta 3 subunit, whereas an extended C-terminal domain does not participate in the inactivation process. Thus, the beta 3 subunit appears to use a rapid inactivation mechanism to produce a current with a relatively rapid apparent activation time course at low Ca2+. The beta 3 subunit is a compelling example of how the beta  subunit family can finely tune the gating properties of Ca2+- and voltage-dependent BK channels.

Key words: accessory subunits; K+ channels; BK channels; Ca2+- and voltage-gated K+ channels; mSlo channels; inactivation


Copyright © 2000 Society for Neuroscience  0270-6474/00/20134890-14$05.00/0


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