Large conductance, voltage- and Ca2+-activated K+ (BK(Ca)) channels regulate blood vessel tone, synaptic transmission, and hearing owing to dual activation by membrane depolarization and intracellular Ca2+. Similar to an archeon Ca2+-activated K+ channel, MthK, each of four alpha subunits of BK(Ca) may contain two cytosolic RCK domains and eight of which may form a gating ring. The structure of...

Background—K channel activation in vascular smooth muscle cells (VSMCs) plays a key role in regulating vascular tone. It has been proposed that endothelium-derived hyperpolarizing factor (EDHF) contributes to microvascular dilation more than nitric oxide (NO) does. Whether hyperpolarization is important for coronary arteriolar dilation in humans is not known. Bradykinin (BK), an endogenous vaso...

High conductance, calcium- and voltage-activated potassium (BK) channels are widely expressed in mammals. In some tissues, the biophysical properties of BK channels are highly affected by coexpression of regulatory (beta) subunits. beta1 and beta2 subunits increase apparent channel calcium sensitivity. The beta1 subunit also decreases the voltage sensitivity of the channel and the beta2 subunit...

The activity (Po) of large-conductance voltage/Ca(2+)-gated K(+) (BK) channels is blunted by cholesterol levels within the range found in natural membranes. We probed BK channel-forming α (cbv1) subunits in phospholipid bilayers with cholesterol and related monohydroxysterols and performed computational dynamics to pinpoint the structural requirements for monohydroxysterols to reduce BK Po and ...

Large conductance calcium-activated potassium (BK) channels are widely expressed in the nervous system. We have recently shown that principal neurons from canine intracardiac ganglia (ICG) express a paxilline- and TEA-sensitive BK current, which increases neuronal excitability. In the present work, we further explore the molecular constituents of the BK current in canine ICG. We found that the ...

Acid-sensing ion channels (ASICs) are neuronal non-voltage-gated cation channels that are activated when extracellular pH falls. They contribute to sensory function and nociception in the peripheral nervous system, and in the brain they contribute to synaptic plasticity and fear responses. Some of the physiologic consequences of disrupting ASIC genes in mice suggested that ASIC channels might m...

High-conductance apical K+ (BK) channels are present in surface colonocytes of mammalian (including human) colon. Their location makes them well fitted to contribute to the excessive intestinal K(+) losses often associated with infective diarrhea. Since many channel proteins are regulated by phosphorylation, we evaluated the roles of protein kinase A (PKA) and phosphatases in the modulation of ...

PURPOSE Anterior chamber structures are subjected to changes in intraocular pressure (IOP). Several studies have pointed out that trabecular meshwork (TM) cells are sensitive to mechanical stretch and that cell-signaling mechanisms are activated in response to elevated pressure. Because membrane stretch has been shown to be a modulator of several ionic conductances, this study was conducted to ...

In this issue, Zeng et al. report results from a series of elegant experiments that, among other contributions, provide new evidence in support of the hypothesis that the BK Ca channel contains two types of high-affinity Ca 2 -binding sites. Those that work with this channel will quickly recognize the significance of these data. To the less well initiated, however, it might seem surprising that...

In the exuberant world of K + channels, the Ca 2+-and voltage-activated K + (BK, MaxiK, Slo1) channel stands alone. It is coded by a single gene (slo1 or KCNMA1), and the pore-forming  subunit has seven transmembrane segments instead of six as found in voltage-dependent K + Being activated by depolarizing voltages and cytoplasmic Ca 2+ , the BK channel is the perfect molecular machine to retar...