ArticleBritish journal of pharmacology2012
PKC-dependent activation of human K(2P) 18.1 K(+) channels.
Article in British journal of pharmacology, 2012. 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, 40 citations in OpenAlex.
- Differential Effects of the Betablockers Carvedilol, Metoprolol and Bisoprolol on Cardiac KInternational journal of molecular sciences · 2023Article
- PKC regulation of ion channels: The involvement of PIPThe Journal of biological chemistry · 2022Review
- Article
- The Background KInternational journal of molecular sciences · 2020Review
- Altered expression and functional role of ion channels in leukemia: bench to bedside.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- Effects of analgesics and antidepressants on TREK-2 and TRESK currents.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2016Article
- The family of K2P channels: salient structural and functional properties.The Journal of physiology · 2015Review
- Properties, regulation, pharmacology, and functions of the K₂p channel, TRESK.Pflugers Archiv : European journal of physiology · 2015Review
- Two-pore domain potassium channels: potential therapeutic targets for the treatment of pain.Pflugers Archiv : European journal of physiology · 2015Review
- Modulation of K2P 2.1 and K2P 10.1 K(+) channel sensitivity to carvedilol by alternative mRNA translation initiation.British journal of pharmacology · 2014Article
- Identification of novel small molecule modulators of K2P18.1 two-pore potassium channel.European journal of pharmacology · 2014Article
- Functional characterization of zebrafish K2P18.1 (TRESK) two-pore-domain K+ channels.Naunyn-Schmiedeberg's archives of pharmacology · 2014Article
- Dopaminergic neurotoxicants cause biphasic inhibition of purinergic calcium signaling in astrocytes.PloS one · 2014Article
- Article
- Over-expression of TRESK K(+) channels reduces the excitability of trigeminal ganglion nociceptors.PloS one · 2014Article
- Functional analysis of a migraine-associated TRESK K+ channel mutation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Protein kinase A and C regulate leak potassium currents in freshly isolated vascular myocytes from the aorta.PloS one · 2013Article
- Novel electrophysiological properties of dronedarone: inhibition of human cardiac two-pore-domain potassium (K2P) channels.Naunyn-Schmiedeberg's archives of pharmacology · 2012Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeTwo-pore-domain K(+) channels (K(2P) ) mediate K(+) background currents that modulate the membrane potential of excitable cells. K(2P) 18.1 (TWIK-related spinal cord K(+) channel) provides hyperpolarizing background currents in neurons. Recently, a dominant-negative loss-of-function mutation in K(2P) 18.1 has been implicated in migraine, and activation of K(2P) 18.1 channels was proposed as a therapeutic strategy. Here we elucidated the molecular mechanisms underlying PKC-dependent activation of K(2P) 18.1 currents. EXPERIMENTAL APPROACH: Human K(2P) 18.1 channels were heterologously expressed in Xenopus laevis oocytes, and currents were recorded with the two-electrode voltage clamp technique. KEY
resultsStimulation of PKC using phorbol 12-myristate-13-acetate (PMA) activated the hK(2P) 18.1 current by 3.1-fold in a concentration-dependent fashion. The inactive analogue 4α-PMA had no effect on channel activity. The specific PKC inhibitors bisindolylmaleimide I, Ro-32-0432 and chelerythrine reduced PMA-induced channel activation indicating that PKC is involved in this effect of PMA. Selective activation of conventional PKC isoforms with thymeleatoxin (100 nM) did not reproduce K(2P) 18.1 channel activation. Current activation by PMA was not affected by pretreatment with CsA (calcineurin inhibitor) or KT 5720 (PKA inhibitor), ruling out a significant contribution of calcineurin or cross-talk with PKA to the PKC-dependent hK(2P) 18.1 activation. Finally, mutation of putative PKC phosphorylation sites did not prevent PMA-induced K(2P) 18.1 channel activation. CONCLUSIONS AND IMPLICATIONS: We demonstrated that activation of hK(2P) 18.1 (TRESK) by PMA is mediated by PKC stimulation. Hence, PKC-mediated activation of K(2P) 18.1 background currents may serve as a novel molecular target for migraine treatment.
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