Enhanced spontaneous Ca2+ events in endothelial cells reflect signalling through myoendothelial gap junctions in pressurized mesenteric arteries

Kansui, Yasuo; Garland, C J; Dora, K A

doi:10.1016/j.ceca.2007.11.012

Cited by 105 publications

(150 citation statements)

References 59 publications

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“…20 The enhancing effect of bradykinin was substantially inhibited in the presence of U-73122 (Figures 2a and e, n ¼ 17). U-73433 (10 À6 mol l À1 ), a negative analog of U-73122, 20 showed no effect (Figures 2b and e, n ¼ 8).…”

Section: Resultsmentioning

confidence: 94%

“…The following drugs were used: bradykinin (10 À7 mol l À1 ), 3 U-73122 (10 À6 mol l À1 ), 20 U-73433 (10 À6 mol l À1 ), 20 cyclopiazonic acid (3 Â 10 À6 mol l À1 ), 21 HC-030031 (5 Â 10 À6 mol l À1 ), 22 H-89 (10 À6 mol l À1 ), 8,23 XE-991 (10 À5 mol l À1 ), 24 bisindolylmaleimide-I (10 À6 mol l À1 ), 25 capsaicin (10 À5 mol l À1 ), 26 capsazepine (5 Â 10 À6 mol l À1 ) 27 and phentolamine (10 À4 mol l À1 ) 28 from Sigma-Aldrich (St Louis, MO, USA) arachidonyl trifluoromethyl ketone (3 Â 10 À5 mol l À1 , AACOCF 3 ) 29 from Calbiochem (San Diego, CA, USA) o-conotoxin GVIA (2 Â 10 À9 or 10 À6 mol l À1 ) 30,31 and Calcitonin Gene-Related Peptide (Human, 8-37) (CGRP8-37, 10 À7 mol l À1 ) 32 from Peptide Institute (Osaka, Japan) and wortmannin (10 À5 mol l À1 ) 33 and AP-18 (10 À6 mol l À1 ) 34 from Biomol (Plymouth Meeting, PA, USA). Stock solutions of bradykinin, phentolamine, oconotoxin GVIA, H-89 and CGRP8-37 were dissolved in distilled water.…”

Section: Drugsmentioning

confidence: 99%

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Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5-bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries

et al. 2012

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Sympathetic nerves regulate vascular tone by releasing neurotransmitters into the vasculature. We previously demonstrated that bradykinin facilitates sympathetic neurotransmission in rat mesenteric arteries. Although little is known about the intracellular mechanism modulating this neurotransmission, recent cell line experiments have shown that the KCNQ channel, which is inhibited by the depletion of membrane phosphatidylinositol-4,5-bisphosphate (PIP 2 ), participates in the control of neurotransmission by bradykinin. In the present study, we examined the mechanism regulating neurotransmitter release from rat perivascular sympathetic nerves. Excitatory junction potentials (EJPs) elicited by repetitive nerve stimulation (1 Hz, 11 pulses, 20 ls, 20-50 V), a measure of sympathetic purinergic neurotransmission, were recorded with a conventional microelectrode technique in rat mesenteric arteries. Bradykinin (10 À7 mol l À1 ) significantly enhanced the amplitude of EJPs (n ¼ 22, Po0.05). This enhancing effect was abolished by N-type calcium-channel inhibition with x-conotoxin GVIA (2 Â 10 À9 mol l À1 , n ¼ 8). The blockade of phospholipase C with U-73122 (10 À6 mol l À1 , n ¼ 17) also eliminated the facilitatory effect of bradykinin. In addition, the effects of bradykinin were diminished by the prevention of PIP 2 resynthesis with wortmannin (10 À5 mol l À1 n ¼ 7) or KCNQ channel inhibition with XE-991 (10 À5 mol l À1 , n ¼ 7). On the other hand, depletion of intracellular calcium stores with cyclopiazonic acid (3 Â 10 À6 mol l À1 , n ¼ 6) or the inhibition of protein kinase C with bisindolylmaleimide-I (10 À6 mol l À1 , n ¼ 9) did not alter the action of bradykinin. These data demonstrate that the hydrolysis of PIP 2 by phospholipase C, which is activated by G q/11 -coupled receptors, and subsequent KCNQ channel inhibition enhance sympathetic purinergic neurotransmission presumably via the activation of N-type calcium channels in rat mesenteric arteries.

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Section: Resultsmentioning

confidence: 94%

Section: Drugsmentioning

confidence: 99%

Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5-bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries

et al. 2012

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“…Block of these intrinsic Ca 2+ pulsars, or of IK Ca channels, depolarizes the adjacent SMC by ∼8 mV, suggesting that the two are functionally linked and continually suppress SMC membrane potential (7). Although ECs in pressurized resistance arteries/arterioles in vivo and in vitro generate spontaneous EC Ca 2+ events, it is not known whether changes in intraluminal pressure influence these events and whether there is a functional consequence against myogenic tone (8)(9)(10).…”

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confidence: 99%

Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca ²⁺ events, and IK _Ca channels, reducing arteriolar tone

Bagher

Beleznai

Kansui

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Endothelial cell (EC) Ca 2+ -activated K channels (SK Ca and IK Ca channels) generate hyperpolarization that passes to the adjacent smooth muscle cells causing vasodilation. IK Ca channels focused within EC projections toward the smooth muscle cells are activated by spontaneous Ca 2+ events (Ca 2+ puffs/pulsars). We now show that transient receptor potential, vanilloid 4 channels (TRPV4 channels) also cluster within this microdomain and are selectively activated at low intravascular pressure. In arterioles pressurized to 80 mmHg, ECs generated low-frequency (∼2 min −1 ) inositol 1,4,5-trisphosphate receptor-based Ca 2+ events. Decreasing intraluminal pressure below 50 mmHg increased the frequency of EC Ca 2+ events twofold to threefold, an effect blocked with the TRPV4 antagonist RN1734. These discrete events represent both TRPV4-sparklet-and nonsparklet-evoked Ca 2+ increases, which on occasion led to intracellular Ca 2+ waves. The concurrent vasodilation associated with increases in Ca 2+ event frequency was inhibited, and basal myogenic tone was increased, by either RN1734 or TRAM-34 (IK Ca channel blocker), but not by apamin (SK Ca channel blocker). These data show that intraluminal pressure influences an endothelial microdomain inversely to alter Ca 2+ event frequency; at low pressures the consequence is activation of EC IK Ca channels and vasodilation, reducing the myogenic tone that underpins tissue blood-flow autoregulation.endothelial cell calcium | cremaster arterioles | mesenteric arteries C a 2+ -activated K + (K Ca ) channels in arteriolar endothelial cells (ECs) are activated by intrinsic spontaneous or receptormediated Ca 2+ events, each leading to hyperpolarization of smooth muscle cells (SMCs) and vasodilation independent of nitric oxide or prostacyclin-the endothelium-dependent hyperpolarization (EDH) response. This hyperpolarization spreads both radially and longitudinally through the vascular wall via patent gap junctions to evoke local and conducted dilation, and it is central to cardiovascular function (1, 2).EDH is the predominant endothelium-dependent mechanism in smaller "resistance" arteries and arterioles. The underlying hyperpolarization is generated by two subtypes of K Ca channels found in the EC, but not SMC, membrane, the small (SK Ca ,K Ca 2.3) and intermediate (IK Ca, K Ca 3.1) conductance forms that may be activated independently of each other (3). The physiological importance of independent activation is apparent from studies with K Ca 3.1-deficient mice in which the mean blood pressure is raised by ∼7 mmHg, but further elevated by disrupting both K Ca channels (4). In mesenteric resistance arteries, IK Ca channels are focused within EC projections through the internal elastic lamina (IEL) termed myoendothelial junctions (MEJs). MEJs can contain gap junctions (MEGJs) coupling ECs to SMCs, and EDH can spread by direct electrical coupling and/or a diffusible factor (5, 6). The IK Ca channels enriched within MEJs can be activated by spontaneous inositol 1,4,5-trisphosphate (IP 3 ...

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“…[188]. Future studies are necessary to understand whether InsP 3 -evoked Ca 2+ mobilization and SOCE are selectively associated to CSE and eNOS, respectively.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide and Endothelial Dysfunction: Relationship with Nitric Oxide

Altaany¹,

Moccia²,

Munaron³

et al. 2014

CMC

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The endothelium is a cellular monolayer that lines the inner surface of blood vessels and plays a central role in the maintenance of cardiovascular homeostasis by controlling platelet aggregation, vascular tone, blood fluidity and fibrinolysis, adhesion and transmigration of inflammatory cells, and angiogenesis. Endothelial dysfunctions are associated with various cardiovascular diseases, including atherosclerosis, hypertension, myocardial infarction, and cardiovascular complications of diabetes. Numerous studies have established the antiinflammatory, anti-apoptotic, and anti-oxidant effects of hydrogen sulfide (H 2 S), the latest member to join the gasotransmitter family along with nitric oxide and carbon monoxide, on vascular endothelium. In addition, H 2 S may prime endothelial cells (ECs) toward angiogenesis and contribute to wound healing, aside to its well-known ability to relax vascular smooth muscle cells (VSMCs), thereby reducing blood pressure. Finally, H 2 S may inhibit VSMC proliferation and platelet aggregation. Consistently, a deficit in H 2 S homeostasis is involved in the pathogenesis of atherosclerosis and of hyperglycaemic endothelial injury. Therefore, the application of H 2 S-releasing drugs or using gene therapy to increase endogenous H 2 S level may help restore endothelial function and antagonize the progression of cardiovascular diseases. The present article reviews recent studies on the role of H 2 S in endothelial homeostasis, under both physiological and pathological conditions, and its putative therapeutic applications. Endothelial structure and functionThe endothelium lines the luminal surface of the entire vascular tree and the cardiac chambers, where it is termed endocardium. As a consequence, the endothelium presents a rather broad extension (300 to 1000 m 2 ) and weight (1.5 kg), achieving sizes comparable to other vital organs of the human body [1,2]. The endothelium can, therefore, be regarded as a real "organ spread across the organism" [3] and, as such, not only it is important for the regulation of local tissue functions, but also for maintaining the whole organism homeostasis [4]. Vascular endothelial cells (ECs) possess a polarized architecture: their luminal membrane is directly exposed to hematic constituents and circulating cells, while the basolateral surface is separated from surrounding tissues by a glycoprotein basement membrane -the sub-endothelial basement -which is formed by fibronectin, laminin, and collagen and is secreted by ECs themselves [2].Heterogeneity is, however, the hallmark of endothelium. ECs differ in morphology, function, and gene expression profile, so that even neighbouring cells from the same organ and blood vessel type exhibit distinct features [4]. For instance, vascular ECs may vary in size, shape, thickness and position of the nucleus. Albeit oriented along direction of blood flow, to attenuate the impact of shear stress forces on the vascular wall, microvascular ECs are rather thin (0.1 µm) and spindle-like, whilst their macrovascul...

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Enhanced spontaneous Ca2+ events in endothelial cells reflect signalling through myoendothelial gap junctions in pressurized mesenteric arteries

Cited by 105 publications

References 59 publications

Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5-bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries

Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5-bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries

Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca ²⁺ events, and IK _Ca channels, reducing arteriolar tone

Hydrogen Sulfide and Endothelial Dysfunction: Relationship with Nitric Oxide

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Enhanced spontaneous Ca2+ events in endothelial cells reflect signalling through myoendothelial gap junctions in pressurized mesenteric arteries

Cited by 105 publications

References 59 publications

Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5-bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries

Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5-bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries

Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca 2+ events, and IK Ca channels, reducing arteriolar tone

Hydrogen Sulfide and Endothelial Dysfunction: Relationship with Nitric Oxide

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Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca ²⁺ events, and IK _Ca channels, reducing arteriolar tone