Involvement of the Na⁺ ,K⁺ -ATPase isoforms in control of cerebral perfusion

What 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.

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 [Ca²⁺ ]_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.