Trafficking of the pore-forming alpha-subunits of large conductance calcium- and voltage-activated potassium (BK) channels to the cell surface represents an important regulatory step in controlling BK channel function. Here, we identify multiple trafficking signals within the intracellular RCK1-RCK2 linker of the cytosolic C terminus of the channel that are required for efficient cell surface e...

The uterorelaxant effect of human chorionic gonadotropin (hCG) is regarded as an important mediator in maintenance of uterine quiescence during pregnancy with clinical potential for tocolysis, the mechanisms of which are unknown. The large conductance calcium-activated K(+) channel (BK(Ca)) is ubiquitously encountered in human uterine tissue and plays a significant role in modulating myometrial...

BK channels modulate neurotransmitter release due to their activation by voltage and Ca(2+). Intracellular Mg(2+) also modulates BK channels in multiple ways with opposite effects on channel function. Previous single-channel studies have shown that Mg(2+) blocks the pore of BK channels in a voltage-dependent manner. We have confirmed this result by studying macroscopic currents of the mslo1 cha...

Large conductance, voltageand Ca 2 -activated K (BK Ca ) channels regulate blood vessel tone, synaptic transmission, and hearing owing to dual activation by membrane depolarization and intracellular Ca 2 . Similar to an archeon Ca 2 -activated K channel, MthK, each of four subunits of BK Ca may contain two cytosolic RCK domains and eight of which may form a gating ring. The structure of the Mth...

Smooth-muscle calcium-activated large-conductance potassium channels (BK channels) are activated by tamoxifen and 17-beta-estradiol. This increase in NP(o), the number of channels, N, multiplied by open probability, depends on the presence of the regulatory beta1-subunit. Furthermore, a previous study indicated that 17-beta-estradiol might bind an extracellular site on the beta1-subunit. Becaus...

The pore-lining amino acids of ion channel proteins reside on the interface between a polar (the pore) and a nonpolar environment (the rest of the protein). The structural dynamics of this region, which physically controls ionic flow, are essential components of channel gating. Using large-conductance, Ca(2+)-dependent K(+) (BK) channels, we devised a systematic charge-substitution method to pr...

Large conductance Ca(2+)- and voltage-activated potassium (BK) channels are comprised of pore-forming α subunits and various regulatory auxiliary subunits. The BK channel auxiliary γ (BKγ) subunits are a newly identified class of proteins containing an extracellular leucine-rich repeat domain (LRRD), a single transmembrane (TM) segment, and a short cytoplasmic C-terminal tail (C-tail). Although...

BK potassium channels regulate spike width and firing rate. A BK point mutation in humans enhances channel activity, leading to epilepsy. In this issue of Neuron, Yang and colleagues use this mutation to demonstrate that channel opening is determined by the flexibility of a region that contains a Ca(2+)-binding site.

A novel vasodilatory influence of endothelial cell (EC) large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels is present following in vivo exposure to chronic hypoxia (CH) and may exist in other pathological states. However, the mechanism of channel activation that results in altered vasoreactivity is unknown. We tested the hypothesis that CH removes an inhibitory effect of the scaffolding ...

The BK-type Ca 2+-activated K + channel has been the subject of increasingly detailed mechanistic study since the fi rst recordings of this channel were obtained more than 25 years ago (Pallotta et al., 1981 ; Latorre et al., 1982 ; Magleby, 2003 ; and references therein). But if you thought that our understanding of the gating of the BK channel and its allosteric regulation by Ca 2+ and trans-...