Functional effects of auxiliary beta4-subunit on rat large-conductance Ca(2+)-activated K(+) channel.
Large-conductance calcium-activated potassium (BK(Ca)) channels are composed of the pore-forming alpha-subunit and the auxiliary beta-subunits. The beta4-subunit is dominantly expressed in the mammalian central nervous system. To understand the physiological roles of the beta4-subunit on the BK(Ca) channel alpha-subunit (Slo), we isolated a full-length complementary DNA of rat beta4-subunit (rbeta4), expressed heterolgously in Xenopus oocytes, and investigated the detailed functional effects using electrophysiological means. When expressed together with rat Slo (rSlo), rbeta4 profoundly altered the gating characteristics of the Slo channel. At a given concentration of intracellular Ca(2+), rSlo/rbeta4 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 rbeta4. Single-channel recordings showed that the increased Hill coefficient for Ca(2+) was due to the changes in the open probability of the rSlo/rbeta4 channel. Single BK(Ca) channels composed of rSlo and rbeta4 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 beta4-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.
Ha
Tal Soo
TS
Department of Life Science, Kwangju Institute of Science and Technology, Gwangju, 500-712, Korea.
Heo
Moon-Sun
MS
Park
Chul-Seung
CS
D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007700:Kinetics; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009474:Neurons / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry*; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011336:Probability; D017434:Protein Structure, Tertiary; D018075:RNA, Complementary / Q000378:metabolism; D051381:Rats; D051637:Shaker Superfamily of Potassium Channels; D014981:Xenopus
D018076:DNA, Complementary; C101877:Kcnab3 protein, mouse; C494840:Kcnab3 protein, rat; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D018075:RNA, Complementary; D051637:Shaker Superfamily of Potassium Channels; D002118:Calcium