We reported evidence of bradykinin (BK) regeneration from C-terminal extended BK sequences that behave as peptidase-activated B2 receptor (B2R) agonists. Further to these in vitro studies, we carried out in vivo experiments to verify hemodynamic effects of BK analogs exhibiting variable susceptibility toward vascular and blood plasma peptidases. Rats were anesthetized and instrumented to record...

Large conductance K(+) (BK) channels are a key determinant of neuronal excitability. Medial vestibular nucleus (MVN) neurons regulate eye movements to ensure image stabilization during head movement, and changes in their intrinsic excitability may play a critical role in plasticity of the vestibulo-ocular reflex. Plasticity of intrinsic excitability in MVN neurons is mediated by kinases, and BK...

Bradykinin (BK) is an endogenous vasoactive peptide that promotes vasodilation by stimulating the release of nitric oxide (NO) from endothelial cells via activation of endothelial NO synthase (eNOS). Although the role of BK in modulation of eNOS activity is well understood, its possible effect on eNOS expression remains uncertain. Several studies have demonstrated negative feedback regulation o...

Aims/hypothesis—Evidence is accumulating that Ca2+-regulated K+ (KCa) channels are important for beta cell function. We used BK channel knockout (BK-KO) mice to examine the role of these KCa channels for glucose homeostasis, beta cell function and viability. Methods—Glucose and insulin tolerance were tested with male wild-type and BK-KO mice. BK channels were detected by single-cell RT-PCR, cyt...

We previously reported that bradykinin (BK; 1-1000 nM) facilitates norepinephrine (NE) release from cardiac sympathetic nerves. Because BK production increases in myocardial ischemia, endogenous BK could foster NE release and associated arrhythmias. We tested this hypothesis in guinea pig and human myocardial ischemia models. BK administration (100 nM) markedly enhanced exocytotic and carrier-m...

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...

We performed a case-control study to determine the association of BK plasma viremia with hemorrhagic cystitis (HC) in hematopoietic cell transplant (HCT) recipients. Thirty cases of HC (14 of which occurred after platelet engraftment with documented BK viruria [BK-HC]) were compared with matched controls. Weekly plasma samples were tested for BK virus DNA by polymerase chain reaction (PCR). BK ...

Large conductance, calcium- and voltage-activated potassium (BK(Ca)) channels are important modulators of pulmonary vascular smooth muscle membrane potential, and phosphorylation of BK(Ca) channels by protein kinases regulates pulmonary arterial smooth muscle function. However, little is known about the effect of phosphorylating specific channel subunits on BK(Ca) channel activity. The present ...

We determined the contribution of vascular large conductance Ca2+-activated K+ (BK) and L-type Ca2+ channel dysregulation to exaggerated mortality in cecal ligation/puncture (CLP)-induced septic BK channel β1-subunit knockout (BK β1-KO, smooth muscle specific) mice. CLP-induced hemodynamic changes and mortality were assessed over 7 days in wild-type (WT) and BK β1-KO mice that were either untre...