Impaired Trafficking of β1 Subunits Inhibits BK Channels in Cerebral Arteries of Hypertensive Rats

Leo, M. Dennis; Zhai, Xue; Yin, Weiqiang; Jaggar, Jonathan H.

doi:10.1161/hypertensionaha.118.11147

Cited by 18 publications

(27 citation statements)

References 43 publications

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“…The increased sensitivity to calcium conferred by the β1 subunit is required for the BK Ca to translate calcium sparks to MP hyperpolarization . Impaired β1 subunits inhibited BK Ca activation in cerebral arteries of hypertensive rats, leading to dysfunctional vasodilation . Disruption and knockout of the BK Ca ‐β1 gene ( KCNMB1 ) were associated with elevated blood pressure in mice, and downregulation of the β1 subunit was been reported in hypertensive rats .…”

Section: Pathophysiological Roles Of Potassium Channelsmentioning

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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Section: Pathophysiological Roles Of Potassium Channelsmentioning

confidence: 99%

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

Doğan

Yıldız

Arslan

et al. 2019

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

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“…Recently, the regulated trafficking of BK channel subunits (including α, β1, and γ subunits) has been accepted as a functional mechanism to modulate arterial contractility. When β1 trafficking is reduced, there is a decrease in BK channel currents and vasoconstriction observed in hypertension [ 158 , 159 ]. In some studies on animal models of hypertension, where there was a treatment with BK Ca channel blockers, exaggerated vasoconstrictor responses were observed, supporting the hypothesis that there is an increased activity of these channels in the presence of the pathology [ 42 , 48 ].…”

Section: Clinical Importance and Medical Uses Of K + mentioning

confidence: 99%

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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“…Endothelin-1 (ET-1) is a vasoconstrictor that activates protein kinase C (PKC) and stimulates PKC-mediated phosphorylation of Rab11A at serine 177. Subsequently, surface β 1 trafficking is reduced, resulting in a decrease in BK channel currents and vasoconstriction [33,34].…”

Section: The Function Of Bk Channel In Diabetes and Hypertensionmentioning

confidence: 99%

Potassium Channels in the Vascular Diseases

Zhu¹,

Jiang²,

Ye³

et al. 2020

Vascular Biology - Selection of Mechanisms and Clinical Applications

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The vessel wall is an intricate structure composed of three layers: the intima (consisting of endothelial cells), media (consisting of smooth muscle cells and elastic fibers), and externa (consisting of the extracellular matrix scaffold). The homeostasis of the vasculature depends on the consistent function of each layer. In the vascular system, potassium channels are well known to regulate vascular function. The interactions between vascular conditions and membrane potential are complicated. In this chapter, we will focus on the functional regulation of KCa channel, K ATP channel, and K V channel in the vascular system. Researchers may continuously obtain insights into the functions of these channels and identify new therapeutic targets for vascular diseases.

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Impaired Trafficking of β1 Subunits Inhibits BK Channels in Cerebral Arteries of Hypertensive Rats

Cited by 18 publications

References 43 publications

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

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

Clinical Importance of the Human Umbilical Artery Potassium Channels

Potassium Channels in the Vascular Diseases

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