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

Familial hemiplegic migraine type2 (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 alpha 2 isoform might be responsible for these biphasic changes in several ways. We found that reduced expression of the alpha 2 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 alpha 2 isoform in astrocytes provides for the possibility of elevated extracellular potassium signalling from astrocytic endfeet to the vascular wall in neurovascular coupling.