5.2 AN ASSOCIATED WITH FAMILIAL HEMIPLEGIC MIGRAINE TYPE 2 MUTATION IN THE ALPHA-2 ISOFORM NA,K-ATPASE DISTURBS VASCULAR RESPONSES IN MOUSE BRAIN

DOI

10.1016/j.artres.2016.10.030How to use a DOI?

Abstract

Objectives: Migraine attack is associated with severe changes in brain perfusion vasoconstriction-induced hypoxemia during aura and rebound vasodilation in subsequent headache. Familial Hemiplegic Migraine Type 2 is associated with point mutations (including G301R) in the α2 isoform Na,K-ATPase. Heterozygote mice bearing G301R mutation (FHM2) were recently characterized for several behavioral and neuronal abnormalities.

Methods: Vascular function of wild type (WT) and FHM2 mice was compared in vivo (telemetry and Laser Speckle measurements of brain perfusion), in vitro (myography) and in situ (changes in astrocytic [Ca²⁺]_iand parenchymal arteriole diameter in brain slices to electric field stimulation (EFS)).

Results: Vascular abnormalities were shown for cerebral circulation while only minor or no significant changes were found in peripheral arteries. Accordingly, no difference in blood pressure was seen under resting conditions. Middle cerebral artery from FHM2 mice had large inner diameter and constricted stronger to U46619, endothelin and K⁺-depolarization. This was associated with increased depolarization and Src-kinase-dependent sensitization to [Ca²⁺]_i.

Isolated cerebral arteries from FHM2 mice have exaggerated relaxation to elevated [K⁺]_out(4–12mM) due to increased role of the inward-rectifying K⁺channels. Repeated EFS (>3 times) reduced the [Ca²⁺]_iresponses in astrocytic endfeet and increased relaxation of parenchymal arterioles in the FHM2 in comparison with WT. Flow responses to whiskers stimulation were also potentiated in FHM2 mice.

Conclusions: A knock-out mutation of the α2 Na,K-ATPase leads to both elevated contractility and increased relaxation of cerebral arteries. These dysfunctions could affect the blood supply to active neurons and thus disturb neurovascular coupling.

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TY  - JOUR
AU  - Christian Staehr
AU  - Lise Hangaard
AU  - Karin Lykke-Hartmann
AU  - Elena Bouzinova
AU  - Christian Aalkjaer
AU  - Vladimir Matchkov
PY  - 2016
DA  - 2016/11/24
TI  - 5.2 AN ASSOCIATED WITH FAMILIAL HEMIPLEGIC MIGRAINE TYPE 2 MUTATION IN THE ALPHA-2 ISOFORM NA,K-ATPASE DISTURBS VASCULAR RESPONSES IN MOUSE BRAIN
JO  - Artery Research
SP  - 57
EP  - 57
VL  - 16
IS  - C
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2016.10.030
DO  - 10.1016/j.artres.2016.10.030
ID  - Staehr2016
ER  -