Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth

Wf, Jackson

doi:10.1016/bs.apha.2016.07.001

Cited by 100 publications

(74 citation statements)

References 441 publications

(544 reference statements)

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“…This observation suggest that in addition to the effect of K + fluxes and their effect of resting V M , the channel protein may be relevant for the signaling leading to proliferation. Upon PM, Kv1.3 channel is the only Kv1 channel whose expression is either preserved or upregulated in all vascular beds explored. In contractile VSMCs, there is a dominant expression of Kv1.5 channels, alone or forming heteromultimers with Kv1.2 channels . As discussed, PM involves active suppression of differentiation markers.…”

Section: Identification Of Kv Channels Contributing To Phenotypic Switchmentioning

confidence: 95%

Kv channels and vascular smooth muscle cell proliferation

2018

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Kv channels are present in virtually all VSMCs and strongly influence contractile responses. However, they are also instrumental in the proliferative, migratory, and secretory functions of synthetic, dedifferentiated VSMCs upon PM. In fact, Kv channels not only contribute to all these processes but also are active players in the phenotypic switch itself. This review is focused on the role(s) of Kv channels in VSMC proliferation, which is one of the best characterized functions of dedifferentiated VSMCs.VSMC proliferation is a complex process requiring specific Kv channels at specific time and locations. Their identification is further complicated by their large diversity and the differences in expression across vascular beds. Of interest, both conserved changes in some Kv channels and vascular bed-specific regulation of others seem to coexist and participate in VSMC proliferation through complementary mechanisms.Such a system will add flexibility to the process while providing the required robustness to preserve this fundamental cellular response. K E Y W O R D Scell cycle regulation, phenotypic modulation, potassium channels, vascular remodeling, vascular smooth muscle cell proliferation | THE MULTIPLE PHENOTYPES OF VASCULAR SMOOTH MUSCLE CELLSVSMCs in the vessel wall express a unique repertoire of contractile proteins, signaling molecules, receptors, and ion channels and exhibit extremely low rates of proliferation, migration, and production of ECM proteins. However, VSMCs maintain significant plasticity even in adult animal. In response to changes in environmental cues, VSMCs switch from their contractile, differentiated phenotype to a dedifferentiated, synthetic, and proliferative phenotype. This process, known as PM or phenotypic switching, entails profound structural and functional changes involving changes in gene expression and signaling mecha- 3-7The contractile state is controlled by multiple transcriptional factors, being SRF the best characterized. SRF binds to a specific cis-element, the CArG box, present in the promoter region of target genes. While most VSMC differentiation marker genes contain one or multiple CArG elements, CArG-SRF complexes can also modulate the expression of proliferation-related genes. 8,9 Specificity of these regulatory mechanisms depends on the expression of myocardin, a SRF coactivator expressed exclusively in SMCs and cardiomyocytes. 10-12Myocardin expression is dramatically reduced in cultured SMC, in contrast to the constant levels of SRF with SMC phenotypic modulation.Understanding myocardin function will permit to understand the normal VSMC differentiation and also PM.13

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Section: Identification Of Kv Channels Contributing To Phenotypic Switchmentioning

confidence: 95%

Kv channels and vascular smooth muscle cell proliferation

2018

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“…K + channels play important role in the regulation of vascular tone. Opening of K + channels results in relaxation due to membrane hyperpolarization . In our study, the vasorelaxant effect of TMB was not affected by pre‐incubation with glibenclamide (an ATP‐sensitive potassium channel blocker), indicating that the relaxant effect of TMB is not related to the opening of ATP‐sensitive K + channels.…”

Section: Discussionmentioning

confidence: 50%

Trimebutine maleate relaxes the isolated rat thoracic aorta: The role of nitric oxide and L‐type calcium channels

Kadıoğlu

Yaşar

Barut

et al. 2019

Clin Exp Pharma Physio

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Trimebutine maleate (TMB), a widely prescribed drug for functional gastrointestinal disorders, has been reported to regulate smooth muscle contractility by modulating multiple ion channel activities in the gastrointestinal tract. However, its action on isolated aorta has not yet been reported. The aim of the present study was to evaluate in vitro vasorelaxant properties and the underlying pharmacological mechanisms of TMB in isolated rat thoracic aortic rings. Vascular activity experiments were performed on thoracic aorta isolated from Sprague-Dawley rats in vitro, including endothelium-intact and endothelium-denuded aortic rings. TMB (10 −10 -10 −5 mol/L) induced relaxation in endothelium-intact aortic rings precontracted by phenylephrine with a potency similar to that of carbachol. TMB-induced relaxation was not altered by glibenclamide and atropine in endothelium-intact aortic rings. However, L-NAME and endothelium denudation significantly reduced but not completely reversed the vasorelaxant effect of TMB. Also, TMB-induced relaxation wasn't affected by diclofenac in endothelium-intact aortic rings. TMB at 10 −5 mol/L significantly reduced the CaCl 2 -induced contractions in endothelium-intact aortic rings stimulated with KCl, but not stimulated with phenylephrine under Ca 2+ free conditions. Moreover, TMB at 10 −5 mol/L effectively attenuated Bay-K8644-induced contractions in aortic rings. These results suggest that TMB-induced relaxation was mediated by both endothelium-dependent and endothelium-independent manner in isolated rat thoracic aorta. The mechanism of TMB-induced relaxation at low concentrations is partially related to NO-and endothelium-dependent but unrelated to prostanoids formation. However, inhibition of Ca 2+ influx through voltage-operated calcium channels and L-type Ca 2+ channel blocking effect appears to be involved in the mechanism of vasorelaxant effect of TMB at high concentrations. K E Y W O R D SBay K8644, L-type calcium channels, nitric oxide, thoracic aorta, trimebutine maleate, vasorelaxant

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“…There are many opportunities for future research on vascular tone regulation through K + channels . Nonetheless, our understanding is lacking about the regional heterogeneity in the nature and composition of K + channels in different vascular beds.…”

Section: Resultsmentioning

confidence: 99%

Potassium channels in vascular smooth muscle: a pathophysiological and pharmacological perspective

Doğan

Yıldız

Arslan

et al. 2019

Fundamemntal Clinical Pharma

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Potassium (K+) ion channel activity is an important determinant of vascular tone by regulating cell membrane potential (MP). Activation of K+ channels leads to membrane hyperpolarization and subsequently vasodilatation, while inhibition of the channels causes membrane depolarization and then vasoconstriction. So far five distinct types of K+ channels have been identified in vascular smooth muscle cells (VSMCs): Ca+2‐activated K+ channels (BKCa), voltage‐dependent K+ channels (KV), ATP‐sensitive K+ channels (KATP), inward rectifier K+ channels (Kir), and tandem two‐pore K+ channels (K2P). The activity and expression of vascular K+ channels are changed during major vascular diseases such as hypertension, pulmonary hypertension, hypercholesterolemia, atherosclerosis, and diabetes mellitus. The defective function of K+ channels is commonly associated with impaired vascular responses and is likely to become as a result of changes in K+ channels during vascular diseases. Increased K+ channel function and expression may also help to compensate for increased abnormal vascular tone. There are many pharmacological and genotypic studies which were carried out on the subtypes of K+ channels expressed in variable amounts in different vascular beds. Modulation of K+ channel activity by molecular approaches and selective drug development may be a novel treatment modality for vascular dysfunction in the future. This review presents the basic properties, physiological functions, pathophysiological, and pharmacological roles of the five major classes of K+ channels that have been determined in VSMCs.

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Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth

Cited by 100 publications

References 441 publications

Kv channels and vascular smooth muscle cell proliferation

Kv channels and vascular smooth muscle cell proliferation

Trimebutine maleate relaxes the isolated rat thoracic aorta: The role of nitric oxide and L‐type calcium channels

Potassium channels in vascular smooth muscle: a pathophysiological and pharmacological perspective

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