TASK-1 channel blockade by AVE1231 increases vasocontractile responses and BP in 1- to 2-week-old but not adult rats.


Journal

British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536

Informations de publication

Date de publication:
11 2020
Historique:
received: 27 02 2020
revised: 14 08 2020
accepted: 18 08 2020
pubmed: 30 8 2020
medline: 22 6 2021
entrez: 30 8 2020
Statut: ppublish

Résumé

The vasomotor role of K2P potassium channels during early postnatal development has never been investigated. We tested the hypothesis that TASK-1 channel (K2P family member) contribution to arterial vascular tone and BP is higher in the early postnatal period than in adulthood. We studied 10- to 15-day-old ("young") and 2- to 3-month-old ("adult") male rats performing digital PCR (dPCR) (using endothelium-intact saphenous arteries), isometric myography, sharp microelectrode technique, quantitative PCR (qPCR) and Western blotting (using endothelium-denuded saphenous arteries), and arterial pressure measurements under urethane anaesthesia. We found mRNA of Kcnk1-Kcnk7, Kcnk12, and Kcnk13 genes to be expressed in rat saphenous artery, and Kcnk3 (TASK-1) and Kcnk6 (TWIK-2) were most abundant in both age groups. The TASK-1 channel blocker AVE1231 (1 μmol·L We showed that TASK-1 channels are important for negative feedback regulation of vasocontraction in young but not adult rats. The influence of TASK-1 channels most likely contributes to low BP level at perinatal age.

Sections du résumé

BACKGROUND AND PURPOSE
The vasomotor role of K2P potassium channels during early postnatal development has never been investigated. We tested the hypothesis that TASK-1 channel (K2P family member) contribution to arterial vascular tone and BP is higher in the early postnatal period than in adulthood.
EXPERIMENTAL APPROACH
We studied 10- to 15-day-old ("young") and 2- to 3-month-old ("adult") male rats performing digital PCR (dPCR) (using endothelium-intact saphenous arteries), isometric myography, sharp microelectrode technique, quantitative PCR (qPCR) and Western blotting (using endothelium-denuded saphenous arteries), and arterial pressure measurements under urethane anaesthesia.
KEY RESULTS
We found mRNA of Kcnk1-Kcnk7, Kcnk12, and Kcnk13 genes to be expressed in rat saphenous artery, and Kcnk3 (TASK-1) and Kcnk6 (TWIK-2) were most abundant in both age groups. The TASK-1 channel blocker AVE1231 (1 μmol·L
CONCLUSION AND IMPLICATIONS
We showed that TASK-1 channels are important for negative feedback regulation of vasocontraction in young but not adult rats. The influence of TASK-1 channels most likely contributes to low BP level at perinatal age.

Identifiants

pubmed: 32860629
doi: 10.1111/bph.15249
pmc: PMC7589011
doi:

Substances chimiques

Nerve Tissue Proteins 0
Potassium Channels 0
Potassium Channels, Tandem Pore Domain 0
potassium channel subfamily K member 3 1HQ3YCN4GS
Methoxamine HUQ1KC1YLI

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5148-5162

Subventions

Organisme : Russian Science Foundation
ID : N 19-15-00210
Organisme : Deutscher Akademischer Austauschdienst

Informations de copyright

© 2020 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

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Auteurs

Anastasia A Shvetsova (AA)

Centre for Biomedicine and Medical Technology Mannheim (CBTM) and European Center of Angioscience (ECAS), Research Division Cardiovascular Physiology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Faculty of Biology, M. V. Lomonosov Moscow State University, Moscow, Russia.

Dina K Gaynullina (DK)

Faculty of Biology, M. V. Lomonosov Moscow State University, Moscow, Russia.

Nadine Schmidt (N)

Centre for Biomedicine and Medical Technology Mannheim (CBTM) and European Center of Angioscience (ECAS), Research Division Cardiovascular Physiology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.

Peter Bugert (P)

Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany.

Elena V Lukoshkova (EV)

Institute of Experimental Cardiology, National Medical Research Center of Cardiology, Moscow, Russia.

Olga S Tarasova (OS)

Faculty of Biology, M. V. Lomonosov Moscow State University, Moscow, Russia.
State Research Center of the Russian Federation-Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia.

Rudolf Schubert (R)

Centre for Biomedicine and Medical Technology Mannheim (CBTM) and European Center of Angioscience (ECAS), Research Division Cardiovascular Physiology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Physiology, Institute of Theoretical Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany.

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Classifications MeSH