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

摘要

A family of accessory β 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 β subunit family, which confers properties on BK channels totally unlike any that have as yet been observed. Coexpression of this subunit (termed β3) with Slo α 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 β3 subunit, whereas an extended C-terminal domain does not participate in the inactivation process. Thus, the β3 subunit appears to use a rapid inactivation mechanism to produce a current with a relatively rapid apparent activation time course at low Ca²⁺. The β3 subunit is a compelling example of how the β subunit family can finely tune the gating properties of Ca²⁺- and voltage-dependent BK channels.