Vladimir Matchkov

Familial hemiplegic migraine type 2 (FHM2) associated mutation in the 2 isoform of Na,KATPase leads to elevated contractility and vasodilatation

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The vasogenic theory of migraine suggests that the aura (a phase preceding the headache and characterized by visual, sensory and/or motor disturbances) is associated with vasoconstrictioninduced hypoxemia in the brain, while the subsequent headache is caused by a rebound vasodilation. FHM 2 is associated with few point mutations in the 2 isoform Na,K-ATPase. Mice bearing a mutation corresponding to the inherited mutation in FHM2 patients (G301R) were used in
functional studies of middle cerebral arteries. Arteries from heterozygote G301R mice were not different in total 2 Na,K-ATPase mRNA in comparison with WT, but 51±11% of their mRNA contained G301R mutation. G301R mice had
elevated blood pressure and unchanged heart rate. Inner diameter of cerebral arteries from G301R mice was larger than in WT. G301R arteries were more sensitive and had higher maximal contraction to U46619, endothelin and K+-depolarization. This was associated with increased depolarization and sensitization to [Ca2+]i (in spite of reduced Ca2+ influx) in G301R arteries.
pNaKtide, a peptide inhibiting the Na,K-ATPase-dependent Src activation, abolished differences between G301R and WT mice. G301R arteries have pronounced relaxation to elevated [K+]out in comparison with WT. This was associated with increased hyperpolarization of smooth muscles which was blocked by 30 μM BaCl2. BaCl2 abolished the difference in relaxations between the groups. G301R arteries had an elevated mRNA of inward rectifying K+ channels, 190±32% of the WT.
In accordance with the vasogenic theory of migraine FHM2 associated mutation of the 2 Na,KATPase leads to both elevated contractility and increased relaxation of cerebral arteries.
Original languageEnglish
Publication yearAug 2014
Number of pages1
Publication statusPublished - Aug 2014
EventPharmacology and Physiology: International Scientific Congress 2014: Pharmacology and Physiology - Putra World Trade Centre, Kuala Lumpur, Malaysia
Duration: 22 Aug 201424 Aug 2014

Conference

ConferencePharmacology and Physiology: International Scientific Congress 2014
LocationPutra World Trade Centre
CountryMalaysia
CityKuala Lumpur
Period22/08/201424/08/2014

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