T16A(inh)-A01, CaCC(inh)-A01 and MONNA are identified as selective inhibitors of the TMEM16A calcium-activated chloride channel (CaCC). The aim this study was to examine chloride-specificity these compounds on isolated resistance arteries in presence absence (±) extracellular chloride.Isolated were maintained a myograph tension recorded, some instances combined with microelectrode impalement for membrane potential measurements or intracellular calcium monitoring using fura-2....

Background: The Fontan procedure has revolutionized the treatment of univentricular hearts. However, it is associated with severe complications such as protein-losing enteropathy, plastic bronchitis, and peripheral edema that may involve lymphatic circulation. We aimed to assess function morphology in patients a Methods: functional state vessels lower extremities circulation (n=10) was investigated using novel technique near-infrared fluorescence imaging compared an age-, sex-,...

Although the biophysical fingerprints (ion selectivity, voltage-dependence, kinetics, etc) of Ca(2+)-activated Cl(-) currents are well established, their molecular identity is still controversial. Several candidates have been suggested; however, none them has fully accepted. We recently characterized a cGMP-dependent current with unique characteristics in smooth muscle cells. This novel shown to coexist "classic" (cGMP-independent) and distinct from those previously known for currents. Here,...

The presence of Ca(2+)-activated Cl(-) channels (CaCCs) in vascular smooth muscle cells (SMCs) is well established. Their molecular identity is, however, elusive. Two distinct currents (I Cl(Ca)) were previously characterized SMCs. We have shown that the cGMP-dependent I Cl(Ca) depends on bestrophin expression, while "classical" not. Downregulation bestrophins did not affect arterial contraction but inhibited rhythmic contractions, vasomotion. In this study, we used vivo siRNA transfection...

Key points We studied the effects of antihypertensive calcium channel blockers on Ca V 1.2, predominantly expressed L‐type in largest human lymphatic vessel, thoracic duct. Human collecting vessels, both large and small, are highly‐sensitive vitro to blockers; exposure these drugs inhibits endogenous contractile activity action potentials diminishes noradrenaline‐induced phasic contractions. In vivo administration blocker nifedipine healthy volunteers did not reduce despite all subjects...

The current study characterizes the mechanical properties of human thoracic duct and demonstrates a role for adrenoceptors, thromboxane, endothelin receptors in lymph vessel function. With ethical permission informed consent, portions (2-5 cm) were resected retrieved at T(7)-T(9) during esophageal cardia cancer surgery. Ring segments (2 mm long) mounted myograph isometric tension (N/m) measurement. diameter-tension relationship was established using ducts from 10 individuals. Peak active...

Key points Initial studies have described the electrical properties of lymphatic smooth muscle cells from different animal species and ion channels contributing to these properties. However, there is a translational gap human situation where on tissue are lacking. Voltage‐gated sodium essential for generation action potentials, thus spontaneous contractions in vessels, but not noradrenaline‐induced contractions. A channel opener elicited as result calcium influx via voltage‐gated...

We investigate sensing and signaling mechanisms for H + , [Formula: see text] CO 2 in basilar arteries using out-of-equilibrium solutions. Selectively varying pH o [[Formula: text]] o, or pCO we find: (a) lowering attenuates vasoconstriction vascular smooth muscle cell (VSMC) Ca 2+ -responses whereas raising augments independently of VSMC [Ca ] i (b) increases arterial agonist-sensitivity tone development without affecting but c) no evidence that has direct net vasomotor effects. Receptor...

In smooth muscle cells, K(+) permeability is high, and this highly influences the resting membrane potential. Lymph propulsion dependent on phasic contractions generated by cells of lymphatic vessels, it likely that channels play a critical role in regulating contractility tissue. The aim study was to investigate contribution distinct human vessel contractility. Thoracic ducts were harvested from 43 patients mounted wire myograph for isometric force measurements or potential recordings with...

Ouabain, a specific inhibitor of the Na + /K -pump, has previously been shown to interfere with intercellular communication. Here we test hypothesis that communication between vascular smooth muscle cells is regulated through an interaction -pump and /Ca 2+ -exchanger leading increase in intracellular calcium concentration ([Ca ] i ) discrete areas near plasma membrane. [Ca was imaged cultured rat aortic cell pairs (A7r5) mesenteric small artery segments simultaneously force. In A7r5...

We have previously characterized a cGMP-dependent Ca2+-activated Cl– current in vascular smooth muscle cells (SMCs) and shown its dependence on bestrophin-3 expression. hypothesize that this is important for synchronization of SMCs the wall. In present study, we aimed to test hypothesis by transfecting rat mesenteric small arteries vivo with siRNA specifically targeting bestrophin-3. The were tested 3 days after transfection vitro isometric force development intracellular Ca2+ SMCs....

Lymphatic vessels from animals have been shown to be innervated. While morphological studies confirmed human lymphatic are innervated, functional supporting this lacking. The present study demonstrates a innervation of the thoracic duct (TD) that is predominantly adrenergic. TDs harvested 51 patients undergoing esophageal and cardia cancer surgery were either fixed for structural investigations or maintained in vitro assessment by isometric force measurements electrical field stimulation...

Objective Cardiovascular diseases have high comorbidity with major depression. Endothelial dysfunction may explain the adverse cardiovascular outcome in depression; therefore, we analyzed it vitro. In chronic mild stress model, some rats develop depression-like symptoms (including "anhedonia"), whereas others are resilient. Methods After 8 weeks of stress, anhedonic reduced their sucrose intake by 55% (7%), resilient did not. Acetylcholine-induced endothelium-dependent relaxation...

Interstitial Cajal-like cells (ICLCs) are speculated to be pacemakers in smooth muscle tissues. While the human thoracic duct (TD) is spontaneously active, origin of this activity unknown. We hypothesized that ICLCs could present TD and using histological techniques, immunohistochemistry immunofluorescence we have investigated presence ICLCs, protein markers for cellular morphology TD. Transmission electron microscopy was employed investigate ultrastructure. Methylene blue staining,...

Human lymphatic vessels are myogenically active and respond to sympathetic stimulation. The role of various cations in this behavior has recently been investigated, but whether the anion Cl- is essential unclear. With ethical approval informed consent, human thoracic duct mesenteric were obtained from surgical patients. Spontaneous or norepinephrine-induced isometric force production isolated was measured by wire myography; transmembrane gradient channels investigated substitution...

The specific role of different isoforms the Na,K-pump in vascular wall is still under debate. We have previously suggested that α(2) isoform (α(2)), Na(+), Ca(2+)-exchange (NCX), and connexin43 form a regulatory microdomain smooth muscle cells (SMCs), which controls intercellular communication contractile properties wall. tested this hypothesis by downregulating cultured SMCs small arteries with siRNA vivo. Intercellular was assessed using membrane capacitance measurements. Arteries...

Objective Major depression and cardiovascular diseases have a strong comorbidity; however, the reason for this is unknown. In chronic mild stress (CMS) model of depression, only fraction rats develop major feature depression—anhedonia-like behavior, whereas other are resilient. Previous studies suggested that CMS also increased total peripheral vascular resistance. Methods On basis CMS-induced changes sucrose intake, reliable measure anhedonia, were divided into “resilient” “anhedonic”...

L-type Ca(2+) channels (LTCCs) are important for vascular smooth muscle cell (VSMC) contraction, as well VSMC differentiation, indicated by loss of LTCCs during dedifferentiation. However, it is not clear whether a primary event underlying phenotypic modulation or has significance structure. We used small interference RNA (siRNA) transfection in vivo to investigate the role expression and structure rat mesenteric arteries. siRNA reduced LTCC mRNA protein arteries 3 days after 12.7 ± 0.7%...

Abstract TMEM 16A is essential for Ca 2+ ‐activated Cl − conductance in vascular smooth muscle. The importance of agonist‐induced constriction and blood pressure control is, however, under debate. Previous studies suggested that might have a complex cellular function beyond being the conductance, example modulation channel expression. Mice with constitutive, muscle‐specific expression si RNA directed against Tmem16a (transgenic mice, TG ) were generated. Isometric constrictions isolated...