Endothelial derived hyperpolarization in renal interlobar arteries.

Jens Christian Brasen, Charlotte M. Sørensen

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Abstract

In small arteries, vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are connect by myoendothelial junctions (MEJ), usually extending from the EC. Ca2+ activated K+ channels (IKCa and SKCa) located in the MEJ are suggested to play a role in NO-independent endothelium derived hyperpolarization (EDH) of VSMCs. The IKCa and SKCa channels could affect the VSMC through direct electrical coupling via myoendothelial gap junctions (MEGJ). Alternatively, K+ released from the EC into the intercellular space between EC and VSMC could activate VSMC Kir and Na/K-ATPases. A spatiotemporal model was constructed to simulate possible effect of IKCa and SKCa activation in MEJ. The model suggested that a significant part of the K+ current entered the VSMC via MEGJ. The simulation also showed that activation of IKCa and SKCa elevated extracellular K+ slightly, which could affect VSMC Kir and Na/K-ATPases. Experiments were conducted in the wire-myograph using renal interlobar arteries from wild-type and Cx40 knock-out mice. NO synthase and the cyclooxygenase were inhibited using L-NAME and indomethacin. The EDH elicited in renal vessels from wild-type and Cx40 knock-out mice were not significantly different. Inhibition of IKCa and SKCa using TRAM-34 and Apamin significantly reduced EDH in renal vessels from both wild-type and Cx40 KO mice. Inhibition of Kir and Na/K-ATPases reduced EDH in Cx40 KO mice but not in wild-type mice. We suggest that EDH consists of at least two independent pathways, K+ current through MEGJs and increased extracellular K+ , which can relay the signal from the IKCa and SKCa channels.
Original languageEnglish
JournalActa Physiologica
Volume215
Issue numberSuppl. 703 - Meeting Abstract
Pages (from-to)3-3
ISSN1748-1708
Publication statusPublished - 2015
EventMeeting on Endothelium-Dependent Hyperpolarizations in Health and Disease - Nyborg, Denmark
Duration: 14 Sep 201517 Sep 2015

Workshop

WorkshopMeeting on Endothelium-Dependent Hyperpolarizations in Health and Disease
Country/TerritoryDenmark
CityNyborg
Period14/09/201517/09/2015

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