Role of endothelial intermediate conductance K<sub>Ca</sub>channels in cerebral EDHF-mediated dilations

Marrelli, Sean P.; Eckmann, Maxim; Hunte, Michael S.

doi:10.1152/ajpheart.00376.2003

Cited by 112 publications

(155 citation statements)

References 54 publications

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“…EDHF-mediated relaxations may involve different subtypes of K ϩ channels in various vascular beds (1,3,7,14). The present study shows that, in rabbit mesenteric arteries, apamin and charybdotoxin partially reduced ACh-induced relaxation, and a combination of both toxins abolished the response.…”

Section: Discussionsupporting

confidence: 49%

“…The EDHF-mediated relaxations involve different subtypes of K ϩ channels. Blockade of the large-conductance Ca 2ϩ -activated K ϩ (K Ca ) channel (BK Ca ) inhibits EDHF-mediated relaxations to ACh in bovine coronary arteries (3), whereas the inhibition of intermediate-conductance K Ca (IK Ca ) channel is sufficient to block EDHF-mediated relaxation in rat cerebral arteries (14). In rat hepatic arteries, stimulation of endothelial cells leads to K ϩ efflux into the myoendothelial space, which causes relaxation by activating inward-rectifying K ϩ (K ir ) channels and Na ϩ -K ϩ -ATPase on the smooth muscle (7).…”

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confidence: 99%

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ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K⁺

Zhang¹,

Gauthier²,

Chawengsub³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Zhang DX, Gauthier KM, Chawengsub Y, Campbell WB. ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K ϩ . Am J Physiol Heart Circ Physiol 293: H152-H159, 2007. First published March 2, 2007; doi:10.1152/ajpheart.00268.2006.-ACh-induced endothelium-dependent relaxation in rabbit small mesenteric arteries is resistant to N-nitro-L-arginine (L-NA) and indomethacin but sensitive to high K ϩ , indicating the relaxations are mediated by endothelium-derived hyperpolarizing factors (EDHFs). The identity of the EDHFs in this vascular bed remains undefined. Small mesenteric arteries pretreated with L-NA and indomethacin were contracted with phenylephrine. ACh (10 Ϫ10 to 10 Ϫ6 M) caused concentration-dependent relaxations that were shifted to the right by lipoxygenase inhibition and the Ca 2ϩ -activated K ϩ channel inhibitors apamin (100 nM) or charybdotoxin (100 nM) and eliminated by the combination of apamin plus charybdotoxin. Relaxations to ACh were also blocked by a combination of barium (200 M) and apamin but not barium plus charybdotoxin. Addition of K ϩ (10.9 mM final concentration) to the preconstricted arteries elicited small relaxations. K ϩ addition before ACh restored the charybdotoxin-sensitive component of relaxations to ACh. K ϩ (10.9 mM) also relaxed endothelium-denuded arteries, and the relaxations were inhibited by barium but not by charybdotoxin and apamin. With the use of whole cell patch-clamp analysis, ACh (10 Ϫ7 M) stimulated voltage-dependent outward K ϩ current from endothelial cells, which was inhibited by charybdotoxin, indicating K ϩ efflux. Arachidonic acid (10 Ϫ7 to 10 Ϫ4 M) induced concentration-related relaxations that were inhibited by apamin but not by charybdotoxin and barium. Addition of arachidonic acid after K ϩ (10.9 mM) resulted in more potent relaxations to arachidonic acid compared with control without K ϩ (5.9 mM). These findings suggest that, in rabbit mesenteric arteries, ACh-induced, L-NA-and indomethacin-resistant relaxation is mediated by endothelial cell K ϩ efflux and arachidonic acid metabolites, and a synergism exists between these two separate mechanisms.acetylcholine; potassium channels; lipoxygenase; endothelium-derived hyperpolarizing factor STIMULATION OF THE VASCULAR endothelium with ACh, bradykinin, and increases in flow induces vasodilation by releasing soluble factors such as nitric oxide (NO), prostacyclin, and endothelium-derived hyperpolarizing factors (EDHFs; see Refs.

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Section: Discussionsupporting

confidence: 49%

mentioning

confidence: 99%

ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K⁺

Zhang¹,

Gauthier²,

Chawengsub³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…Therefore, in the maternal uterine vasculature of pregnant rats, IK Ca channels play a predominant role in mediating endothelial K ϩ currents and in controlling the associated vasodilation. A prevalent role of endothelial IK Ca over SK Ca channels in generating K ϩ currents was also demonstrated in rat cerebral and human mesenteric arteries (35,39). Both IK Ca and SK Ca channels importantly contribute to the generation of Ca 2ϩ -activated currents in single ECs of rat parenchymal arteries (29).…”

Section: Discussionmentioning

confidence: 89%

Impairment of IK_Cachannels contributes to uteroplacental endothelial dysfunction in rat diabetic pregnancy

Gokina

Bonev

Phillips

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Gokina NI, Bonev AD, Phillips J, Gokin AP, Veilleux K, Oppenheimer K, Goloman G. Impairment of IK Ca channels contributes to uteroplacental endothelial dysfunction in rat diabetic pregnancy. Am J Physiol Heart Circ Physiol 309: H592-H604, 2015. First published June 19, 2015 doi:10.1152/ajpheart.00901.2014.-Diabetes in rat pregnancy is associated with impaired vasodilation of the maternal uteroplacental vasculature. In the present study, we explored the role of endothelial cell (EC) Ca 2ϩ -activated K ϩ channels of small conductance (SK Ca channels) and intermediate conductance (IKCa channels) in diabetes-induced uterine vascular dysfunction. Diabetes was induced by injection of streptozotocin to second-day pregnant rats and confirmed by the development of maternal hyperglycemia. Control rats were injected with citrate buffer. Changes in smooth muscle cell intracellular Ca 2ϩ concentration, membrane potential, and vasodilation induced by SK Ca/IKCa channel activators were studied in uteroplacental arteries of control and diabetic rats. The impact of diabetes on SK Ca-and IKCa-mediated currents was explored in freshly dissociated ECs. NS309 evoked a potent vasodilation that was effectively inhibited by TRAM-34 but not by apamin. NS309-induced smooth muscle cell intracellular Ca 2ϩ concentration, membrane potential, and dilator responses were significantly diminished by diabetes; N-cyclohexyl-N-2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4pyrimidinamine (CyPPA)-evoked responses were not affected. Ca 2ϩ -activated ion currents in ECs were insensitive to paxilline, markedly inhibited by charybdotoxin (ChTX), and diminished by apamin. NS309-induced EC currents were generated mostly due to activation of ChTX-sensitive channels. Maternal diabetes resulted in a significant reduction in ChTX-sensitive currents with no effect on apaminsensitive or CyPPA-induced currents. We concluded that IK Ca channels play a prevalent role over SK Ca channels in the generation of endothelial K ϩ currents and vasodilation of uteroplacental arteries.

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“…Agonist-induced endothelial hyperpolarization is mediated by both IKCa (KCa3.1) and SKCa (KCa2.3) channels in many kinds of vessels (Bychkov et al, 2002;Eichler et al, 2003;Gluais et al, 2005;Si et al, 2006). In some vascular beds, however, only IKCa channels have been reported to be responsible (human mesenteric artery, Köhler et al, 2000; rat cerebral artery, Marrelli et al, 2003). The relatively thick portions of guinea-pig mesenteric artery that we used seem to belong to the latter group.…”

Section: Discussionmentioning

confidence: 89%

Analysis of acetylcholine-induced membrane responses in vascular endothelial cells of the guinea-pig mesenteric artery using mefloquine as a gap junction blocker

Yamamoto

Suzuki

2010

J. Smooth Muscle Res.

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Acetylcholine (ACh)-induced membrane currents were investigated using freshly isolated endothelial layers prepared from the guinea-pig mesenteric artery. Gap junctions were blocked by mefloquine and the whole-cell patch clamp method was applied to individual endothelial cells within each multicellular preparation. While mefloquine effectively blocked the gap junctions, it hyperpolarized the membrane by some 10 mV. As this hyperpolarization was absent when the intracellular Cl -concentration was increased, mefloquine may increase the membrane conductance for Cl -. Besides this minor hyperpolarizing effect, mefloquine did not have serious side effects and ACh could activate a sustained outward current producing a membrane hyperpolarization at concentrations as low as 100 nM. At the beginning of ACh application, the reversal potential of the AChinduced current was around the equilibrium potential for K + indicating that this was a K + current. The reversal potential then gradually became less negative suggesting that other ionic conductances with less negative equilibrium potentials were involved. As the AChinduced outward current was completely blocked by charybdotoxin (CTX, 100 nM), this current seemed to be due to CTX-sensitive K + channels, possibly IKCa channels. After the K + current had been blocked, ACh gradually activated the membrane current which reversed the polarity at around -10 mV, which was most likely due to Ca 2+ -activated nonselective cation channels. These ionic conductances may be responsible for the variety in agonist-induced membrane responses observed in different types of vascular preparations.

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Role of endothelial intermediate conductance K_Cachannels in cerebral EDHF-mediated dilations

Abstract: Marrelli, Sean P., Maxim S. Eckmann, and Michael S. Hunte. Role of endothelial intermediate conductance KCa channels in cerebral EDHF-mediated dilations.

Cited by 112 publications

References 54 publications

ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K⁺

ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K⁺

Impairment of IK_Cachannels contributes to uteroplacental endothelial dysfunction in rat diabetic pregnancy

Analysis of acetylcholine-induced membrane responses in vascular endothelial cells of the guinea-pig mesenteric artery using mefloquine as a gap junction blocker

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Role of endothelial intermediate conductance KCachannels in cerebral EDHF-mediated dilations

Abstract: Marrelli, Sean P., Maxim S. Eckmann, and Michael S. Hunte. Role of endothelial intermediate conductance KCa channels in cerebral EDHF-mediated dilations.

Cited by 112 publications

References 54 publications

ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K+

ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K+

Impairment of IKCachannels contributes to uteroplacental endothelial dysfunction in rat diabetic pregnancy

Analysis of acetylcholine-induced membrane responses in vascular endothelial cells of the guinea-pig mesenteric artery using mefloquine as a gap junction blocker

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Product

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Role of endothelial intermediate conductance K_Cachannels in cerebral EDHF-mediated dilations

ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K⁺

ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K⁺

Impairment of IK_Cachannels contributes to uteroplacental endothelial dysfunction in rat diabetic pregnancy