Rectification and rapid activation at low Ca2+ of Ca2+-activated, voltage-dependent BK currents: Consequences of rapid inactivation by a novel beta subunit

A family of accessory beta subunits significantly contributes to the functi onal diversity of large-conductance, Ca2+- and voltage-dependent potassium (BK) channels in native cells. Here we describe the functional properties o f one variant of the b subunit family, which confers properties on BK chann els totally unlike any that have as yet been observed. Coexpression of this subunit (termed beta 3) with S/o alpha subunits results in rectifying outw ard currents and, at more positive potentials, rapidly inactivating (simila r to 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 exami ned. In part because of the rapid inactivation process, single channel open ings are exceedingly brief. Although variance analysis suggests a conductan ce in excess of 160 pS, fully resolved single channel openings are not obse rved. The inactivation process results from a cytosolic N-terminal domain o f the b3 subunit, whereas an extended C-terminal domain does not participat e in the inactivation process. Thus, the b3 subunit appears to use a rapid inactivation mechanism to produce a current with a relatively rapid apparen t activation time course at low Ca2+. The beta 3 subunit is a compelling ex ample of how the b subunit family can finely tune the gating properties of Ca2+- and voltage-dependent BK channels.