ArticleBritish journal of pharmacology2014
Modulation of K2P 2.1 and K2P 10.1 K(+) channel sensitivity to carvedilol by alternative mRNA translation initiation.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- KPharmaceuticals (Basel, Switzerland) · 2026Review
- The two-pore KAmerican journal of physiology. Heart and circulatory physiology · 2025Article
- Rational design, synthesis, and evaluation of novel polypharmacological compounds targeting NaThe Journal of biological chemistry · 2025Article
- Electrophysiological Effects of the Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitor Dapagliflozin on Human Cardiac Potassium Channels.International journal of molecular sciences · 2024Article
- Research progress of two-pore potassium channel in myocardial ischemia-reperfusion injury.Frontiers in physiology · 2024Review
- Differential Effects of the Betablockers Carvedilol, Metoprolol and Bisoprolol on Cardiac KInternational journal of molecular sciences · 2023Article
- Progress on role of ion channels of cardiac fibroblasts in fibrosis.Frontiers in physiology · 2023Review
- Direct Regulation of Hyperpolarization-Activated Cyclic-Nucleotide Gated (HCN1) Channels by Cannabinoids.Frontiers in molecular neuroscience · 2022Article
- Two-Pore-Domain Potassium (KCells · 2021Review
- Block of TREK and TRESK K2P channels by lamotrigine and two derivatives sipatrigine and CEN-092.Biochemistry and biophysics reports · 2021Article
- Bepridil, a class IV antiarrhythmic agent, can block the TREK-1 potassium channel.Annals of translational medicine · 2021Article
- Intracellular activation of full-length human TREK-1 channel by hypoxia, high lactate, and low pH denotes polymodal integration by ischemic factors.Pflugers Archiv : European journal of physiology · 2021Article
- Pharmacological Approaches to Studying Potassium Channels.Handbook of experimental pharmacology · 2021Review
- Translating Translation to Mechanisms of Cardiac Hypertrophy.Journal of cardiovascular development and disease · 2020Review
- Article
- An early nonsense mutation facilitates the expression of a short isoform of CNGA3 by alternative translation initiation.Experimental eye research · 2018Article
- Treatment with HC-070, a potent inhibitor of TRPC4 and TRPC5, leads to anxiolytic and antidepressant effects in mice.PloS one · 2018Article
- Pharmacogenetic diversification by alternative translation initiation: background channels to the fore: Commentary on Kisselbach et al., Br J Pharmacol 171: 5182-5194.British journal of pharmacology · 2015Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe β-receptor antagonist carvedilol blocks a range of ion channels. K2P 2.1 (TREK1) and K2P 10.1 (TREK2) channels are expressed in the heart and regulated by alternative translation initiation (ATI) of their mRNA, producing functionally distinct channel variants. The first objective was to investigate acute effects of carvedilol on human K2P 2.1 and K2P 10.1 channels. Second, we sought to study ATI-dependent modulation of K2P K(+) current sensitivity to carvedilol. EXPERIMENTAL APPROACH: Using standard electrophysiological techniques, we recorded currents from wild-type and mutant K2P 2.1 and K2P 10.1 channels in Xenopus oocytes and HEK 293 cells. KEY
resultsCarvedilol concentration-dependently inhibited K2P 2.1 channels (IC50 ,oocytes = 20.3 μM; IC50 , HEK = 1.6 μM) and this inhibition was frequency-independent. When K2P 2.1 isoforms generated by ATI were studied separately in oocytes, the IC50 value for carvedilol inhibition of full-length channels (16.5 μM) was almost 5-fold less than that for the truncated channel variant (IC50 = 79.0 μM). Similarly, the related K2P 10.1 channels were blocked by carvedilol (IC50 ,oocytes = 24.0 μM; IC50 , HEK = 7.6 μM) and subject to ATI-dependent modulation of drug sensitivity. CONCLUSIONS AND IMPLICATIONS: Carvedilol targets K2P 2.1 and K2P 10.1 K(+) channels. This previously unrecognized mechanism supports a general role of cardiac K2P channels as antiarrhythmic drug targets. Furthermore, the work reveals that the sensitivity of the cardiac ion channels K2P 2.1 and K2P 10.1 to block was modulated by alternative mRNA translation initiation.
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