Clinical Importance of the Human Umbilical Artery Potassium Channels

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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Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+channels in human umbilical artery smooth muscle cells

Channels ◽

10.4161/chan.20362 ◽

2012 ◽

Vol 6 (3) ◽

pp. 174-180 ◽

Cited By ~ 9

Author(s):

Pedro Martín ◽

Nicolás Enrique ◽

Ana R. Roldán Palomo ◽

Alejandro Rebolledo ◽

Veronica Milesi

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Umbilical Artery ◽

Muscle Cells ◽

K Channels ◽

Human Umbilical Artery

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Coupling of Voltage Sensing to Channel Opening Reflects Intrasubunit Interactions in Kv Channels

The Journal of General Physiology ◽

10.1085/jgp.200409194 ◽

2004 ◽

Vol 125 (1) ◽

pp. 71-80 ◽

Cited By ~ 11

Author(s):

Alain J. Labro ◽

Adam L. Raes ◽

Dirk J. Snyders

Keyword(s):

Voltage Dependence ◽

Voltage Sensing ◽

Α Subunit ◽

K Channels ◽

Voltage Gated ◽

Kv Channels ◽

Channel Opening ◽

Subunit Stoichiometry ◽

Voltage Dependent ◽

Tetrameric Structure

Voltage-gated K+ channels play a central role in the modulation of excitability. In these channels, the voltage-dependent movement of the voltage sensor (primarily S4) is coupled to the (S6) gate that opens the permeation pathway. Because of the tetrameric structure, such coupling could occur within each subunit or between adjacent subunits. To discriminate between these possibilities, we analyzed various combinations of a S4 mutation (R401N) and a S6 mutation (P511G) in hKv1.5, incorporated into tandem constructs to constrain subunit stoichiometry. R401N shifted the voltage dependence of activation to negative potentials while P511G did the opposite. When both mutations were introduced in the same α-subunit of the tandem, the positive shift of P511G was compensated by the negative shift of R401N. With each mutation in a separate subunit of a tandem, this compensation did not occur. This suggests that for Kv channels, the coupling between voltage sensing and gating reflects primarily an intrasubunit interaction.

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Review: Evolutionary link between prokaryotic and eukaryotic K+ channels.

Journal of Experimental Biology ◽

10.1242/jeb.201.20.2791 ◽

1998 ◽

Vol 201 (20) ◽

pp. 2791-2799

Author(s):

C Derst ◽

A Karschin

Keyword(s):

Membrane Proteins ◽

Plasma Membranes ◽

Sequence Data ◽

Reducing Power ◽

Eukaryotic Cell ◽

K Channel ◽

K Channels ◽

Coding Regions ◽

Kv Channels ◽

Voltage Dependent

Considering the importance of K+ channels in controlling the crucial K+ gradient across the plasma membranes of all living cells, it comes as no surprise that, besides being present in every eukaryotic cell, these integral membrane proteins have recently also been identified in prokaryotes. Today, approximately a dozen successfully completed and many more ongoing sequencing projects permit a search for genes related to K+ channels in the genomes of both eubacteria and archaea. The coding regions of homologues show a remarkable variety in primary structure. They predict membrane proteins with one, two, three and six hydrophobic segments surrounding a putative K+-selective pore (H5) and the presence or absence of a cytosolic putative NAD+-binding domain (PNBD) that probably senses the reducing power of the cell. The analysis of kinships on the basis of phylogenetic algorithms identifies sequences closely related to eukaryotic voltage-dependent Kv channels, but also defines members of a primordial class of prokaryotic K+ channel (containing the 2TMS/PNBD motif). Considering the unique mechanisms that may account for the assembly of modern proteins from different ancestral genes, and with more primary sequence data soon to appear, a scheme for the evolutionary origin of K+ channels comes within reach.

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154 Effects of raloxifene, tamoxifene and ?-oestradiol on angiotensin type 1 receptor expression in human umbilical artery endothelial cells incubated with high concentrations of glucose

European Heart Journal ◽

10.1016/s0195-668x(03)93699-2 ◽

2003 ◽

Vol 24 (5) ◽

pp. 14

Author(s):

T FRANCUZ

Keyword(s):

Endothelial Cells ◽

Umbilical Artery ◽

Receptor Expression ◽

Human Umbilical Artery ◽

High Concentrations ◽

Angiotensin Type

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Atypical antipsychotic olanzapine inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells

Pharmacological Reports ◽

10.1007/s43440-021-00299-z ◽

2021 ◽

Author(s):

Minji Kang ◽

Jin Ryeol An ◽

Mi Seon Seo ◽

Hee Seok Jung ◽

Ryeon Heo ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Atypical Antipsychotic ◽

Muscle Cells ◽

Arterial Smooth Muscle ◽

K Channels ◽

Voltage Dependent ◽

Arterial Smooth Muscle Cells

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UV-B filter octylmethoxycinnamate impaired the main vasorelaxant mechanism of human umbilical artery

Chemosphere ◽

10.1016/j.chemosphere.2021.130302 ◽

2021 ◽

Vol 277 ◽

pp. 130302

Author(s):

Margarida Lorigo ◽

Carla Quintaneiro ◽

Cláudio J. Maia ◽

Luiza Breitenfeld ◽

Elisa Cairrao

Keyword(s):

Umbilical Artery ◽

Human Umbilical Artery

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Activation and Two Modes of Blockade by Strontium of Ca2+-activated K+ Channels in Goldfish Saccular Hair Cells

The Journal of General Physiology ◽

10.1085/jgp.111.2.363 ◽

1998 ◽

Vol 111 (2) ◽

pp. 363-379 ◽

Cited By ~ 11

Author(s):

Izumi Sugihara

Keyword(s):

Dissociation Constant ◽

Time Constant ◽

Hair Cells ◽

Single Channel ◽

Hill Coefficient ◽

K Channels ◽

Voltage Dependent ◽

Time Courses ◽

The Hill ◽

Inside Out

Effects of internal Sr2+ on the activity of large-conductance Ca2+-activated K+ channels were studied in inside-out membrane patches from goldfish saccular hair cells. Sr2+ was approximately one-fourth as potent as Ca2+ in activating these channels. Although the Hill coefficient for Sr2+ was smaller than that for Ca2+, maximum open-state probability, voltage dependence, steady state gating kinetics, and time courses of activation and deactivation of the channel were very similar under the presence of equipotent concentrations of Ca2+ and Sr2+. This suggests that voltage-dependent activation is partially independent of the ligand. Internal Sr2+ at higher concentrations (>100 μM) produced fast and slow blockade both concentration and voltage dependently. The reduction in single-channel amplitude (fast blockade) could be fitted with a modified Woodhull equation that incorporated the Hill coefficient. The dissociation constant at 0 mV, the Hill coefficient, and zd (a product of the charge of the blocking ion and the fraction of the voltage difference at the binding site from the inside) in this equation were 58–209 mM, 0.69–0.75, 0.45–0.51, respectively (n = 4). Long shut events (slow blockade) produced by Sr2+ lasted ∼10–200 ms and could be fitted with single-exponential curves (time constant, τl−s) in shut-time histograms. Durations of burst events, periods intercalated by long shut events, could also be fitted with single exponentials (time constant, τb). A significant decrease in τb and no large changes in τl−s were observed with increased Sr2+ concentration and voltage. These findings on slow blockade could be approximated by a model in which single Sr2+ ions bind to a blocking site within the channel pore beyond the energy barrier from the inside, as proposed for Ba2+ blockade. The dissociation constant at 0 mV and zd in the Woodhull equation for this model were 36–150 mM and 1–1.8, respectively (n = 3).

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Characterization of contractile adrenoceptors in the human umbilical artery

European Journal of Pharmacology ◽

10.1016/0014-2999(95)00277-r ◽

1995 ◽

Vol 282 (1-3) ◽

pp. 95-101 ◽

Cited By ~ 12

Author(s):

Gunilla Bodelsson ◽

Martin Stjernquist

Keyword(s):

Umbilical Artery ◽

Human Umbilical Artery

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Block of squid axon K channels by internally and externally applied barium ions.

The Journal of General Physiology ◽

10.1085/jgp.80.5.663 ◽

1982 ◽

Vol 80 (5) ◽

pp. 663-682 ◽

Cited By ~ 110

Author(s):

C M Armstrong ◽

R P Swenson ◽

S R Taylor

Keyword(s):

Time Constant ◽

Recovery Time ◽

Pulse Voltage ◽

Squid Axon ◽

Barium Ions ◽

K Channels ◽

Voltage Dependent ◽

One Step ◽

Dissociation Constant Kd ◽

The Way

We have studied the interactions of Ba ion with K channels. Ba2+ blocks these channels when applied either internally or externally in millimolar concentrations. Periodic depolarizations enhance block with internal Ba2+, but diminish the block caused by external Ba2+. At rest, dissociation of Ba2+ from blocked channels is very slow, as ascertained by infrequent test pulses applied after washing Ba2+ form either inside or outside. The time constant for recovery from internal and external Ba2+ is the same. Frequent pulsing greatly shortens recovery time constant after washing away both Ba2+in and Ba2+out. Block by Ba2+ applied internally or externally is voltage dependent. Internal Ba2+ block behaves like a one-step reaction governed by a dissociation constant (Kd) that decreases e-fold/12 mV increase of pulse voltage: block deepens with more positive pulse voltage. For external Ba2+, Kd decreases e-fold/18 mV as holding potential is made more negative: block deepens with increasing negativity. Millimolar external concentrations of some cations can either lessen (K+) or enhance (NH+4, Cs+) block by external Ba2+. NH+4 apparently enhances block by slowing exist of Ba ions from the channels. Rb+ and Cs+ also slow clearing of Ba ions from channels. We think that (a) internally applied Ba2+ moves all the way through the channels, entering only when activation gates are open; (b) externally applied Ba2+ moves two-thirds of the way in, entering predominantly when activation gates are closed; (c) at a given voltage, Ba2+ occupies the same position in the channels whether it entered from inside or outside.

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