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Involvement of the Na + ,K + ‐ATPase isoforms in control of cerebral perfusion
Author(s) -
Staehr Christian,
Rajanathan Rajkumar,
Matchkov Vladimir V.
Publication year - 2019
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/ep087519
Subject(s) - familial hemiplegic migraine , gene isoform , vasoconstriction , cerebral circulation , perfusion , medicine , cerebral blood flow , atpase , endocrinology , extracellular , neuroscience , vasodilation , biology , chemistry , microbiology and biotechnology , biochemistry , migraine , enzyme , migraine with aura , aura , gene
New FindingsWhat is the topic of this review? In this review, we consider the role of the Na + ,K + ‐ATPase in cerebrovascular function and how it might be changed in familial hemiplegic migraine type 2 (FHM2). The primary focus is involvement of the Na + ,K + ‐ATPase isoforms in regulation of cerebrovascular tone.What advances does it highlight? In this review, we discuss three overall distinct mechanisms whereby the Na + ,K + ‐ATPase might be capable of regulating cerebrovascular tone. Furthermore, we discuss how changes in the Na + ,K + ‐ATPase in cerebral arteries might affect brain perfusion and thereby be involved in the pathology of FHM2.Abstract Familial hemiplegic migraine type 2 (FHM2) has been characterized by biphasic changes in cerebral blood flow during a migraine attack, with initial hypoperfusion followed by abnormal hyperperfusion of the affected hemisphere. We suggested that FHM2‐associated loss‐of‐function mutation(s) in the Na + ,K + ‐ATPase α2 isoform might be responsible for these biphasic changes in several ways. We found that reduced expression of the α2 isoform leads to sensitization of the contractile machinery to [Ca 2+ ] i via Src kinase‐dependent signal transduction. This change in sensitivity might be the underlying mechanism for both abnormally potentiated vasoconstriction and exaggerated vasorelaxation. Moreover, the functional significance of the Na + ,K + ‐ATPase α2 isoform in astrocytes provides for the possibility of elevated extracellular potassium signalling from astrocytic endfeet to the vascular wall in neurovascular coupling.