Biophysical Journal
Volume 86, Issue 5, May 2004, Pages 2871-2882
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Functional Effects of Auxiliary β4-Subunit on Rat Large-Conductance Ca2+-Activated K+ Channel

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Abstract

Large-conductance calcium-activated potassium (BKCa) 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 BKCa channel α-subunit (Slo), we isolated a full-length complementary DNA of rat β4-subunit (rβ4), expressed heterolgously in Xenopus oocytes, and investigated the detailed functional effects using electrophysiological means. When expressed together with rat Slo (rSlo), rβ4 profoundly altered the gating characteristics of the Slo channel. At a given concentration of intracellular Ca2+, rSlo/rβ4 channels were more sensitive to transmembrane voltage changes. The activation and deactivation rates of macroscopic currents were decreased in a Ca2+-dependent manner. The channel activation by Ca2+ became more cooperative by the coexpression of rβ4. Single-channel recordings showed that the increased Hill coefficient for Ca2+ was due to the changes in the open probability of the rSlo/rβ4 channel. Single BKCa channels composed of rSlo and rβ4 also exhibited slower kinetics for steady-state gating compared with rSlo channels. Dwell times of both open and closed events were significantly increased. Because BKCa 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.

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