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

Doğan, Muhammed Fatih; Yıldız, Oğuzhan; Arslan, Seyfullah Oktay; Ulusoy, Kemal Gokhan

doi:10.1111/fcp.12461

Cited by 90 publications

(80 citation statements)

References 224 publications

(287 reference statements)

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“…These channels play an important role in regulating the resting membrane potential (MP) and vessel contractility—a role that depends on the vascular bed. Therefore, the physiological MP range in SMCs is essential to understand the K + channel’s role in smooth muscle (SM) [ 1 ]. Overall, vascular SMCs have an MP ranging from −40 and −60 mV, depending on the type of blood vessel [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…When E K is substantially more negative than MP, the opening of K + -channels induces the K + efflux into the extracellular medium, which can cause hyperpolarization or repolarization of the cell membrane, closure of the voltage-gated Ca 2+ -channels (VGCCs), decrease in calcium (Ca 2+ )-entry into the cell, and vasodilatation. On the contrary, the closing of K + -channels can cause depolarization, opening of VGCCs, increase of intracellular Ca 2+ , and vasoconstriction [ 1 , 2 , 4 , 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Clinical Importance of the Human Umbilical Artery Potassium Channels

Lorigo

Oliveira

2020

Cells

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Potassium (K+) channels are usually predominant in the membranes of vascular smooth muscle cells (SMCs). These channels play an important role in regulating the membrane potential and vessel contractility—a role that depends on the vascular bed. Thus, the activity of K+ channels represents one of the main mechanisms regulating the vascular tone in physiological and pathophysiological conditions. Briefly, the activation of K+ channels in SMC leads to hyperpolarization and vasorelaxation, while its inhibition induces depolarization and consequent vascular contraction. Currently, there are four different types of K+ channels described in SMCs: voltage-dependent K+ (KV) channels, calcium-activated K+ (KCa) channels, inward rectifier K+ (Kir) channels, and 2-pore domain K+ (K2P) channels. Due to the fundamental role of K+ channels in excitable cells, these channels are promising therapeutic targets in clinical practice. Therefore, this review discusses the basic properties of the various types of K+ channels, including structure, cellular mechanisms that regulate their activity, and new advances in the development of activators and blockers of these channels. The vascular functions of these channels will be discussed with a focus on vascular SMCs of the human umbilical artery. Then, the clinical importance of K+ channels in the treatment and prevention of cardiovascular diseases during pregnancy, such as gestational hypertension and preeclampsia, will be explored.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical Importance of the Human Umbilical Artery Potassium Channels

Lorigo

Oliveira

2020

Cells

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“…Alternatively, polyphenols are now increasingly considered to exert pharmacological actions through protein-mediated mechanisms. For instance, several polyphenols were shown to modulate therapeutic targets such as voltage-gated L-type Ca 2+ channels and major signalling cascades including the mitogen-activated protein kinases/ extracellular signal-regulated kinases (MAPK/ERK) pathway [5][6][7][8][9][10][11][12][13]. The activation of the two related protein-serine/threonine kinases ERK1 and ERK2 (ERK1/2) requires phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

Urolithin C increases glucose‐induced ERK activation which contributes to insulin secretion

Toubal

Oiry

Bayle

et al. 2020

Fundamemntal Clinical Pharma

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Polyphenols exert pharmacological actions through protein‐mediated mechanisms and by modulating intracellular signalling pathways. We recently showed that a gut‐microbial metabolite of ellagic acid named urolithin C is a glucose‐dependent activator of insulin secretion acting by facilitating L‐type Ca2+ channel opening and Ca2+ influx into pancreatic β‐cells. However, it is still unknown whether urolithin C regulates key intracellular signalling proteins in β‐cells. Here, we report that urolithin C enhanced glucose‐induced extracellular signal‐regulated kinases 1/2 (ERK1/2) activation as shown by higher phosphorylation levels in INS‐1 β‐cells. Interestingly, inhibition of ERK1/2 with two structurally distinct inhibitors led to a reduction in urolithin C effect on insulin secretion. Finally, we provide data to suggest that urolithin C‐mediated ERK1/2 phosphorylation involved insulin signalling in INS‐1 cells. Together, these data indicate that the pharmacological action of urolithin C on insulin secretion relies, in part, on its capacity to enhance glucose‐induced ERK1/2 activation. Therefore, our study extends our understanding of the pharmacological action of urolithin C in β‐cells. More generally, our findings revealed that urolithin C modulated the activation of key multifunctional intracellular signalling kinases which participate in the regulation of numerous biological processes.

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“…In the current issue of Fundamental & Clinical Pharmacology , Dogan et al. reviewed the remodeling of vascular K + channels occurring in major vascular diseases. Indeed, Dogan et al.…”

mentioning

confidence: 99%

“…Indeed, Dogan et al. referred to the studies from the last two decades that described a down‐expression or a downregulation of a variety of K + channels resulting in the depolarization of vascular SMC and associated to pathological phenotype in pulmonary arterial hypertension (PAH) as well as in systemic hypertension, hypercholesterolemia, atherosclerosis and diabetes mellitus.…”

mentioning

confidence: 99%