Functional Effects of Auxiliary β4-Subunit on Rat Large-Conductance Ca 2+-Activated K + Channel

Abstract

Large-conductance calcium-activated potassium (BK Ca) channels are composed of the pore-forming α-subunit and the auxiliary β-subunits. The β4-subunit is dominantly expressed in the mammalian central nervous system. To understand the physiological roles of the β4-subunit on the BK Ca channel α-subunit (Slo), we isolated a full-length complementary DNA of rat β4-subunit (r β4), expressed heterolgously in Xenopus oocytes, and investigated the detailed functional effects using electrophysiological means. When expressed together with rat Slo (rSlo), r β4 profoundly altered the gating characteristics of the Slo channel. At a given concentration of intracellular Ca 2+, rSlo/r β4 channels were more sensitive to transmembrane voltage changes. The activation and deactivation rates of macroscopic currents were decreased in a Ca 2+-dependent manner. The channel activation by Ca 2+ became more cooperative by the coexpression of r β4. Single-channel recordings showed that the increased Hill coefficient for Ca 2+ was due to the changes in the open probability of the rSlo/r β4 channel. Single BK Ca channels composed of rSlo and r β4 also exhibited slower kinetics for steady-state gating compared with rSlo channels. Dwell times of both open and closed events were significantly increased. Because BK Ca channels are known to modulate neuroexcitability and the expression of the β4-subunit is highly concentrated in certain subregions of brain, the electrophysiological properties of individual neurons should be affected profoundly by the expression of this second subunit.