Large-conductance voltage- and calcium-activated potassium (BK) channels have been shown to play a role in detrusor overactivity (DO). The goal of this study was to determine whether bladder outlet obstruction-induced DO is associated with downregulation of BK channels and whether BK channels affect myosin light chain 20 (MLC(20)) phosphorylation in detrusor smooth muscle (DSM). Partial bladder...

Estrogen replacement therapies have been suggested to be beneficial in alleviating symptoms of overactive bladder. However, the precise regulatory mechanisms of estrogen in urinary bladder smooth muscle (UBSM) at the cellular level remain unknown. Large conductance voltage- and Ca2+-activated K+ (BK) channels, which are key regulators of UBSM function, are suggested to be non-genomic targets of...

BACKGROUND Exposure of patients with atopic asthma to allergens produces a long term increase in exhaled nitric oxide (FENO), probably reflecting inducible NO synthase (NOS) expression. In contrast, bradykinin (BK) rapidly reduces FENO. It is unknown whether BK suppresses increased FENO production after allergen exposure in asthma, and whether it modulates FENO via NOS inhibition. METHODS Lev...

Neuronal calcium-activated potassium channels of the BK type are activated by membrane depolarization and intracellular Ca(2+) ions. It has been suggested that these channels may play a key neuroprotective role during and after brain ischemia, but this hypothesis has so far not been tested by selective BK-channel manipulations in vivo. To elucidate the in vivo contribution of neuronal BK channe...

Activation of the renal kallikrein-kinin system results in natriuresis and diuresis, suggesting its possible role in renal tubular sodium transport regulation. Here, we used patch-clamp electrophysiology to directly assess the effects of bradykinin (BK) on the epithelial Na(+) channel (ENaC) activity in freshly isolated split-opened murine aldosterone-sensitive distal nephrons (ASDNs). BK acute...

Inhibitors of ACE/kininase II enhance insulin sensitivity, an action that is mediated in part by bradykinin (BK). We investigated whether insulin interacts with the BK receptor signaling to modulate the inositol 1,4,5-trisphosphate (IP3) response to BK in L8 rat skeletal myoblasts. Stimulation of the cultures with BK (10 nmol/l) for 15 s increased IP3 from a basal level of 75.2 +/- 7.6 to 200.2...

RATIONALE The large conductance Ca(2+)-activated K(+) (BK) channel, a key determinant of vascular tone, is regulated by angiotensin II (Ang II) type 1 receptor signaling. Upregulation of Ang II functions and downregulation of BK channel activities have been reported in diabetic vessels. However, the molecular mechanisms underlying Ang II-mediated BK channel modulation, especially in diabetes me...

Large-conductance voltage- and Ca(2+)-activated K(+) (Slo1 BK) channels serve numerous cellular functions, and their dysregulation is implicated in various diseases. Drugs activating BK channels therefore bear substantial therapeutic potential, but their deployment has been hindered in part because the mode of action remains obscure. Here we provide mechanistic insight into how the dehydroabiet...

Prakriya, Murali and Christopher J. Lingle. Activation of BK channels in rat chromaffin cells requires summation of Ca influx from multiple Ca channels. J Neurophysiol 84: 1123–1135, 2000. Large-conductance Ca and voltage-dependent K channels (BK channels) in many tissues require high Ca concentrations for activation and therefore might be expected to be tightly coupled to Ca channels. However,...

At birth, the lung environment changes from low to relatively high O 2 tension. Pulmonary blood flow increases and pulmonary artery pressure decreases. Recent data suggests that pulmonary vascular calcium-sensitive potassium channel (BK Ca) activation mediates perinatal pulmonary vasodilation. While BK Ca channel expression is developmentally regulated, the molecular mechanisms responsible for ...