Key result
Large quaternary ammonium molecules such as decyltriethylammonium and tetrabutylammonium have much faster block and unblock rates in BK channels compared with other potassium channels, suggesting an enlarged cavity and inner pore.
BK channels have unique inner pore properties with an enlarged cavity that allows fast block/unblock by large quaternary ammonium molecules, potentially explaining their large conductance.
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Enlarged BK channel pores remain an animal-model observation; leaves open selective modulator design for human channelopathies.
Potassium channels have a very wide distribution of single-channel conductance, with BK type Ca(2+)-activated K(+) channels having by far the largest. Even though crystallographic views of K(+) channel pores have become available, the structural basis underlying BK channels' large conductance has not been completely understood. In this study we use intracellularly applied quaternary ammonium compounds to probe the pore of BK channels. We show that molecules as large as decyltriethylammonium (C(10)) and tetrabutylammonium (TBA) have much faster block and unblock rates in BK channels when compared with any other tested K(+) channel types. Additionally, our results suggest that at repolarization large QA molecules may be trapped inside blocked BK channels without slowing the overall process of deactivation. Based on these findings we propose that BK channels may differ from other K(+) channels in its geometrical design at the inner mouth, with an enlarged cavity and inner pore providing less spatially restricted access to the cytoplasmic solution. These features could potentially contribute to the large conductance of BK channels.
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Li et al. (2004) studied this question. Quaternary ammonium compounds (C10 and TBA) vs. Control (unblocked channels) was evaluated on Block and unblock rates of BK channels. Large quaternary ammonium molecules such as decyltriethylammonium and tetrabutylammonium have much faster block and unblock rates in BK channels compared with other potassium channels, suggesting an enlarged cavity and inner pore.
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