Electrophysiological Characterization of Benzofuroindole- Induced Potentiation of Large-Conductance Ca 2ϩ -Activated K ϩ Channels

ABSTRACT Large-conductance Ca 2ϩ -activated K ϩ (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 Ca 2ϩ . The EC 50 and Hill coefficient for rat BK Ca channel ␣ subunit, rSlo, were estimated as 8.9 Ϯ 1.5 M 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 dosedependent 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