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

New Findings

What is the topic of this review? This review considers 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 will be involvement of the Na,K‐ATPase isoforms in regulation of cerebrovascular tone. What advances does it highlight? The review discusses three overall distinct mechanisms whereby the Na,K‐ATPase might be capable of regulating cerebrovascular tone. Furthermore, it discusses how changes in the Na,K‐ATPase in cerebral arteries might affect brain perfusion and thereby be involved in the FHM2 pathology.

Abstract

FHM2 has been characterized by biphasic changes in cerebral blood flow during a migraine attack; 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 may 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 intracellular Ca²⁺ ([Ca²⁺]_i) via Src kinase dependent signal transduction. This change in sensitivity may be the underlying mechanism for both abnormally potentiated vasoconstriction and exaggerated vasorelaxation. Moreover, functional significance of the Na,K‐ATPase α2 isoform in astrocytes provides for the possibility of elevated extracellular potassium signaling from astrocytic endfeet to the vascular wall in neurovascular coupling.

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