Large conductance, Ca(2+)-activated K channel proteins are involved in a wide range of physiological activities, so there is considerable interest in the pharmacology of large conductance calcium-activated K (BK) channels. One potent activator of BK channels is mallotoxin (MTX), which produces a very large hyperpolarizing shift of the voltage gating of heterologously expressed BK channels and c...

BK (Maxi-K) channel activity is allosterically regulated by a Ca2+ sensor, formed primarily by the channel's large cytoplasmic carboxyl tail segment, and a voltage sensor, formed by its transmembrane helices. As with other voltage-gated K channels, voltage sensing in the BK channel is accomplished through interactions of the S1-S4 transmembrane segments with the electric field. However, the BK ...

Scornik FS, Bucciero RS, Wu Y, Selga E, Bosch Calero C, Brugada R, Pérez GJ. DiBAC4(3) hits a “sweet spot” for the activation of arterial large-conductance Ca -activated potassium channels independently of the 1-subunit. Am J Physiol Heart Circ Physiol 304: H1471–H1482, 2013. First published March 29, 2013; doi:10.1152/ajpheart.00939.2012.—The voltage-sensitive dye bis-(1,3-dibutylbarbituric ac...

The large conductance Ca 2 -activated K channel (BK Ca ) is well positioned to assume diverse physiological functions because it is ubiquitously expressed in many cell types. Some of the functions recently proposed for this channel offer unexpected surprises, however, such as a role in innate immunity in neutrophil leukocytes (Ahluwalia et al., 2004), recognition as a heme-binding protein (Tang...

The cortical collecting duct (CCD), which is involved in renal potassium (K) excretion, expresses cytochrome P450 (CYP)-epoxygenase. Here, we examined the effect of high dietary K on renal expression of CYP2C23 and CYP2J2 in the rat, as well as the role of CYP-epoxygenase-dependent metabolism of arachidonic acid in the regulation of Ca(2+)-activated big-conductance K (BK) channels. By Western b...

Activity of the vascular large conductance Ca(2+)-activated K(+) (BK) channel is tightly regulated by its accessory β(1) subunit (BK-β(1)). Downregulation of BK-β(1) expression in diabetic vessels is associated with upregulation of the forkhead box O subfamily transcription factor-3a (FOXO-3a)-dependent F-box-only protein (FBXO) expression. However, the upstream signaling regulating this proces...

Large-conductance, Ca(2+)-activated K(+) channels, commonly referred to as BK channels, have a major role in flow-induced K(+) secretion in the distal nephron. With-no-lysine kinase 4 (WNK4) is a serine-threonine kinase expressed in the distal nephron that inhibits ROMK activity and renal K(+) secretion. WNK4 mutations have been described in individuals with familial hyperkalemic hypertension (...

The molecular mechanisms underlying increased arterial tone during hypertension are unclear. In vascular smooth muscle, localized Ca release events through ryanodine-sensitive channels located in the sarcoplasmic reticulum (Ca sparks) activate large-conductance, Ca -sensitive K (BK) channels. Ca sparks and BK channels provide a negative feedback mechanism that hyperpolarizes smooth muscle and t...

Spontaneous miniature outward currents (SMOCs) in parasympathetic neurons from mudpuppy cardiac ganglia are caused by activation of TEA- and iberiotoxin-sensitive, Ca(2+)-dependent K(+) (BK) channels. Previously we reported that SMOCs are activated by Ca(2+)-induced Ca(2+) release (CICR) from caffeine- and ryanodine-sensitive intracellular Ca(2+) stores. In the present study, we analyzed the si...

The contribution of the large conductance, Ca2+-modulated, voltage-gated K+ channel current, IBK, to the total current during an action potential (AP) from suprachiasmatic nucleus (SCN) neurons is described using a novel computational approach. An experimental recording of an SCN AP and the corresponding AP-clamp recording of IBK from the literature were both digitized. The AP data set was appl...