Pharmacological Approaches to Studying Potassium Channels

Mathie, Alistair; Veale, Emma L.; Golluscio, Alessia; Holden, Robyn G; Walsh, Yvonne

doi:10.1007/164_2021_502

Cited by 15 publications

(19 citation statements)

References 143 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The TREK-1 and -2 and TRAAK channels are commonly activated by polyunsaturated fatty acids such as arachidonic acid (AA) [ 24 , 26 ]. The facilitating effect of Ech A was also observed when activated by arachidonic acid (AA, 10 μM).…”

Section: Resultsmentioning

confidence: 99%

“…Ion channels in sensory nerve endings and certain types of immune cells in the skin also serve as interesting targets for controlling various skin diseases and peripheral pain [ 2 , 20 , 21 , 22 , 23 ]. A number of voltage-independent K2P K + channel (KCNK) family with characteristic two-pore domains in the protomer, such as TREK, TRAAK, and TASK, are known to set the resting membrane potential of the nociceptive sensory neurons [ 24 , 25 , 26 ]. The K2P channels, noticeably TREK-2, are also expressed in skin keratinocytes [ 10 ] and immune cells [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Multiple Effects of Echinochrome A on Selected Ion Channels Implicated in Skin Physiology

et al. 2023

View full text Add to dashboard Cite

Echinochrome A (Ech A), a naphthoquinoid pigment from sea urchins, is known to have anti-inflammatory and analgesic effects that have been suggested to be mediated by antioxidant activity and intracellular signaling modulation. In addition to these mechanisms, the ion channels in keratinocytes, immune cells, and nociceptive neurons may be the target for the pharmacological effects. Here, using the patch clamp technique, we investigated the effects of Ech A on the Ca2+-permeable TRPV3, TRPV1 and Orai1 channels and the two-pore domain K+ (K2P) channels (TREK/TRAAK, TASK-1, and TRESK) overexpressed in HEK 293 cells. Ech A inhibited both the TRPV3 and Orai1 currents, with IC50 levels of 2.1 and 2.4 μM, respectively. The capsaicin-activated TRPV1 current was slightly augmented by Ech A. Ech A alone did not change the amplitude of the TREK-2 current (ITREK2), but pretreatments with Ech A markedly facilitated ITREK2 activation by 2-APB, arachidonic acid (AA), and acidic extracellular pH (pHe). Similar facilitation effects of Ech A on TREK-1 and TRAAK were observed when they were stimulated with 2-APB and AA, respectively. On the contrary, Ech A did not affect the TRESK and TASK-1 currents. Interestingly, the ITREK2 maximally activated by the combined application of 2-APB and Ech A was not inhibited by norfluoxetine but was still completely inhibited by ruthenium red. The selective loss of sensitivity to norfluoxetine suggested an altered molecular conformation of TREK-2 by Ech A. We conclude that the Ech A-induced inhibition of the Ca2+-permeable cation channels and the facilitation of the TREK/TRAAK K2P channels may underlie the analgesic and anti-inflammatory effects of Ech A.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multiple Effects of Echinochrome A on Selected Ion Channels Implicated in Skin Physiology

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Potassium-selective ion channels are pore-forming proteins that allow the flow of potassium ions (K + ) across the plasma membrane. K + channels regulate a cell’s excitability and resting membrane potential and determine the shape of the action potential waveform in cells such as neurons and myocytes ( Mathie et al, 2021 ). K + channel families are classified into four groups: voltage-gated K (Kv), calcium-activated (K Ca ), inwardly rectifying K (Kir), and two-pore domain potassium (K2P) channels ( Taura et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…The most important subfamilies include the classical Kir channels (strong inward-rectifier K + channel/Kir2.x), G-protein-activated Kir channels (GIRK, Kir3.x), ATP-sensitive K + channels (K ATP , Kir6.x), and K + transport channels (Kir1.x, Kir4.x, Kir5.x, and Kir7.x) ( Tian et al, 2014 ). Kir channels are critical in the control of cellular excitability and K + ion homeostasis ( Mathie et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Interaction of Medicinal Plants and Their Active Constituents With Potassium Ion Channels: A Systematic Review

Rajabian

Babaei

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Potassium ion (K+) channels are pore-forming transmembrane proteins that control the transport of K+ ions. Medicinal plants are widely used as complementary therapies for several disorders. Studies have shown that the modulation of K+ channels is most likely involved in various pharmacological effects of medicinal plants. This review aimed to evaluate the modulatory effects of medicinal plants and their active constituents on K+ channels under pathological conditions. This systematic review was prepared according to the Preferred Reporting Items for the Systematic Reviews and Meta-analyses (PRISMA) 2020 guideline. Four databases, including PubMed, Web of Science, embase, and Scopus, were searched. We identified 687 studies from these databases, from which we selected 13 in vivo studies for the review by using the Population, Intervention, Comparison, Outcomes, Study (PICOS) tool. The results of the 13 selected studies showed a modulatory effect of medicinal plants or their active constituents on ATP-sensitive potassium channels (KATP), and small (SKCa) and large (BKCa) conductance calcium-activated K+ channels in several pathological conditions such as nociception, brain ischemia, seizure, diabetes, gastric ulcer, myocardial ischemia-reperfusion, and hypertension via possible involvement of the nitric oxide/cyclic GMP pathway and protein kinase. K+ channels should be considered as significant therapeutic milestones in the treatment of several diseases. We believe that understanding the mechanism behind the interaction of medicinal plants with K+ channels can facilitate drug development for the treatment of various K+ channel-related disorders.

show abstract

“…Their activity regulates several biological processes, including control of neuronal excitability, heart rate, electrolytic balance, and cell division [ 4 , 5 ]. Given their wide localization, diverse structural arrays, and multiple physiological functions, Kv channel malfunctions are associated with several diseases and, consequently, are considered ideal drug discovery targets [ 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

The Kv10.1 Channel: A Promising Target in Cancer

Luis

Anaya-Hernández

León-Sánchez

et al. 2022

IJMS

View full text Add to dashboard Cite

Carcinogenesis is a multistage process involving the dysregulation of multiple genes, proteins, and pathways that make any normal cell acquire a cancer cell phenotype. Therefore, it is no surprise that numerous ion channels could be involved in this process. Since their discovery and subsequent cloning, ion channels have been established as therapeutic targets in excitable cell pathologies (e.g., cardiac arrhythmias or epilepsy); however, their involvement in non-excitable cell pathologies is relatively recent. Among all ion channels, the voltage-gated potassium channels Kv10.1 have been established as a promising target in cancer treatment due to their high expression in tumoral tissues compared to low levels in healthy tissues.

show abstract

Pharmacological Approaches to Studying Potassium Channels

Cited by 15 publications

References 143 publications

Multiple Effects of Echinochrome A on Selected Ion Channels Implicated in Skin Physiology

Multiple Effects of Echinochrome A on Selected Ion Channels Implicated in Skin Physiology

Interaction of Medicinal Plants and Their Active Constituents With Potassium Ion Channels: A Systematic Review

The Kv10.1 Channel: A Promising Target in Cancer

Contact Info

Product

Resources

About