Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway

Cidad, Pilar; Miguel-Velado, Eduardo; Ruiz-McDavitt, Christian; Alonso, E.; Jiménez-Pérez, Laura; Asuaje, Agustín; Carmona, Yamila; García-Arribas, Daniel; López, Javier; Fernández, Mirella; Roqué, Mercè; Pérez-Garcı́a, M. Teresa; López‐López, Jose R.

doi:10.1007/s00424-014-1607-y

Cited by 33 publications

(64 citation statements)

References 46 publications

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“…Proliferation and migration of VSM cells in this model can be attenuated by selective blockade of K V 1.3 channels (Cheong et al, 2011; Cidad et al, 2010). Studies in human VSM cells also confirm a role for K V 1.3 in proliferation (Cheong et al, 2011; Cidad et al, 2015). Interestingly, K V 1.3 may contribute to VSM proliferation by ion-permeation-independent mechanisms (Cidad et al, 2012; Cidad et al, 2015; Jimenez-Perez et al, 2016).…”

Section: K+ Channels and Vsm Proliferationmentioning

confidence: 81%

“…In contrast, balloon-injury of mouse arteries results in upregulation of K V 1.3 (locus: KCNE3 ) (Cidad et al, 2010) and downregulation of K V 1.5 (Cidad et al, 2012; Cidad et al, 2015; Cidad et al, 2014). Proliferation and migration of VSM cells in this model can be attenuated by selective blockade of K V 1.3 channels (Cheong et al, 2011; Cidad et al, 2010).…”

Section: K+ Channels and Vsm Proliferationmentioning

confidence: 98%

“…Increased intracellular Ca 2+ concentration is an important signal for cell proliferation (Bi et al, 2013; Munoz et al, 2013; Urrego et al, 2014). As noted above, other roles for K + channels are also possible (Cidad et al, 2012; Cidad et al, 2015; Urrego et al, 2014). …”

Section: K+ Channels and Vsm Proliferationmentioning

confidence: 98%

“…H. Liu et al, 2009; Mahaut-Smith, Martinez-Pinna, & Gurung, 2008; Okada, Yanagisawa, & Taira, 1993; Urena, del Valle-Rodriguez, & Lopez-Barneo, 2007; Yamagishi, Yanagisawa, & Taira, 1992; Yamamura, Ohya, Muraki, & Imaizumi, 2012; Yanagisawa, Yamagishi, & Okada, 1993). Potassium channels also contribute to the regulation of proliferation of VSM cells through membrane potential-dependent (Bi et al, 2013; Miguel-Velado et al, 2005; Miguel-Velado et al, 2010) and membrane potential-independent mechanisms (Cidad et al, 2012; Cidad et al, 2015; Jimenez-Perez et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

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Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth

2017

Advances in Pharmacology

100

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Potassium channels importantly contribute to the regulation of vascular smooth muscle (VSM) contraction and growth. They are the dominant ion conductance of the VSM cell membrane and importantly determine and regulate membrane potential. Membrane potential, in turn, regulates the open-state probability of voltage-gated Ca2+ channels (VGCC), Ca2+ influx through VGCC, intracellular Ca2+ and VSM contraction. Membrane potential also affects release of Ca2+ from internal stores and the Ca2+ sensitivity of the contractile machinery such that K+ channels participate in all aspects of regulation of VSM contraction. Potassium channels also regulate proliferation of VSM cells through membrane potential-dependent and membrane potential-independent mechanisms. Vascular smooth muscle cells express multiple isoforms of at least five classes of K+ channels contribute to the regulation of contraction and cell proliferation (growth). This review will examine the structure, expression and function of large-conductance, Ca2+-activated K+ (BKCa) channels, intermediate-conductance Ca2+-activated K+ (KCa3.1) channels, multiple isoforms of voltage-gated K+ (KV) channels, ATP-sensitive K+ (KATP) channels, and inward-rectifier K+ (KIR) channels in both contractile and proliferating VSM cells.

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Section: K+ Channels and Vsm Proliferationmentioning

confidence: 81%

Section: K+ Channels and Vsm Proliferationmentioning

confidence: 98%

Section: K+ Channels and Vsm Proliferationmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth

2017

Advances in Pharmacology

100

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“…Further support for this view has recently been provided by our demonstration that upon inhibition of mitochondrial oxidative phosphorylation, AMPK directly phosphorylates K v 1.5 channels, and inhibits K + currents carried by Kv1.5 in pulmonary arterial myocytes [24]. This is evident from the fact that down-regulation of K v 1.5 expression and activity is a hallmark not only of hypoxic pulmonary vasoconstriction but also of pulmonary hypertension [154–162], and may contribute to increased survival of smooth muscle cells due to attenuation of K + channel-dependent apoptosis [163–165] and also facilitate the phenotypic switch from a contractile to a proliferative state [166,167]. …”

Section: In Elliptical Orbit–ampk and The Regulation Of Blood Flow Anmentioning

confidence: 99%

The emerging role of AMPK in the regulation of breathing and oxygen supply

Evans

Mahmoud

Moral-Sanz

et al. 2016

Biochemical Journal

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Regulation of breathing is critical to our capacity to accommodate deficits in oxygen availability and demand during, for example, sleep and ascent to altitude. It is generally accepted that a fall in arterial oxygen increases afferent discharge from the carotid bodies to the brainstem and thus delivers increased ventilatory drive, which restores oxygen supply and protects against hypoventilation and apnoea. However, the precise molecular mechanisms involved remain unclear. We recently identified as critical to this process the AMP-activated protein kinase (AMPK), which is key to the cell-autonomous regulation of metabolic homoeostasis. This observation is significant for many reasons, not least because recent studies suggest that the gene for the AMPK-α1 catalytic subunit has been subjected to natural selection in high-altitude populations. It would appear, therefore, that evolutionary pressures have led to AMPK being utilized to regulate oxygen delivery and thus energy supply to the body in the short, medium and longer term. Contrary to current consensus, however, our findings suggest that AMPK regulates ventilation at the level of the caudal brainstem, even when afferent input responses from the carotid body are normal. We therefore hypothesize that AMPK integrates local hypoxic stress at defined loci within the brainstem respiratory network with an index of peripheral hypoxic status, namely afferent chemosensory inputs. Allied to this, AMPK is critical to the control of hypoxic pulmonary vasoconstriction and thus ventilation–perfusion matching at the lungs and may also determine oxygen supply to the foetus by, for example, modulating utero-placental blood flow.

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Voltage‐dependent conformational changes of Kv1.3 channels activate cell proliferation

Cidad

Alonso

Arévalo-Martínez

et al. 2020

Journal Cellular Physiology

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The voltage-dependent potassium channel Kv1.3 has been implicated in proliferation in many cell types, based on the observation that Kv1.3 blockers inhibited proliferation. By modulating membrane potential, cell volume, and/or Ca 2+ influx, K + channels can influence cell cycle progression. Also, noncanonical channel functions could contribute to modulate cell proliferation independent of K + efflux. The specificity of the requirement of Kv1.3 channels for proliferation suggests the involvement of molecule-specific interactions, but the underlying mechanisms are poorly identified. Heterologous expression of Kv1.3 channels in HEK cells has been shown to increase proliferation independently of K + fluxes. Likewise, some of the molecular determinants of Kv1.3-induced proliferation have been located in the C-terminus region, where individual point mutations of putative phosphorylation sites (Y447A and S459A) abolished Kv1.3-induced proliferation. Here, we investigated the mechanisms linking Kv1.3 channels to proliferation exploring the correlation between Kv1.3 voltage-dependent molecular dynamics and cell cycle progression. Using transfected HEK cells, we analyzed both the effect of changes in resting membrane potential on Kv1.3-induced proliferation and the effect of mutated Kv1.3 channels with altered voltage dependence of gating. We conclude that voltage-dependent transitions of Kv1.3 channels enable the activation of proliferative pathways. We also found that Kv1.3 associated with IQGAP3, a scaffold protein involved in proliferation, and that membrane depolarization facilitates their interaction. The functional contribution of Kv1.3-IQGAP3 interplay to cell proliferation was demonstrated both in HEK cells and in vascular smooth muscle cells. Our data indicate that voltage-dependent conformational changes of Kv1.3 are an essential element in Kv1.3-induced proliferation.

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Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway

Cited by 33 publications

References 46 publications

Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth

Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth

The emerging role of AMPK in the regulation of breathing and oxygen supply

Voltage‐dependent conformational changes of Kv1.3 channels activate cell proliferation

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