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Electrophysiological Characterization of Benzofuroindole-Induced Potentiation of Large-Conductance Ca²⁺-Activated K⁺ Channels

Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, Korea

Large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels are widely distributed and play key roles in various cell functions. We previously reported the chemical synthesis of several benzofuroindole compounds that act as potent openers of BK_Ca channels. In this study, we investigated the mechanism of channel potentiation by one of the compounds, 7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (TBIC), using electrophysiological means. This chemical highly activated cloned BK_Ca channels from extracellular side independent of subunits and regardless of the presence of intracellular Ca²⁺. The EC₅₀ and Hill coefficient for rat BK_Ca channel subunit, rSlo, were estimated as 8.9 ± 1.5 µM and 0.9, respectively. TBIC shifted the conductance-voltage curve of rSlo channels to more hyperpolarized potentials without altering its voltage dependence. Single-channel recording revealed that TBIC increased the open probability of the channel in a dose-dependent manner without any changes in single-channel conductance. Strong potentiation by TBIC was also observed for native BK_Ca channels from rat hippocampus pyramidal neurons. Thus, TBIC and the related benzofuroindole compounds can be useful tools to unravel the mechanism of this novel allosteric activation of BK_Ca channels.

Address correspondence to: Dr. Chul-Seung Park, Department of Life Science, Gwangju Institute of Science and Technology, 1 Oryrong-dong, Bukgu, Gwangju, 500-712, Korea. E-mail: cspark{at}gist.ac.kr