TY - JOUR

T1 - Involvement of the Na + ,K +-ATPase isoforms in control of cerebral perfusion

AU - Staehr, Christian

AU - Rajanathan, Rajkumar

AU - Matchkov, Vladimir V.

PY - 2019

Y1 - 2019

N2 - New Findings: 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. 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.

AB - New Findings: 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. 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.

KW - blood vessels

KW - Na ,K -ATPase

KW - neurovascular coupling

UR - http://www.scopus.com/inward/record.url?scp=85062791072&partnerID=8YFLogxK

U2 - 10.1113/EP087519

DO - 10.1113/EP087519

M3 - Journal article

C2 - 30768809

AN - SCOPUS:85062791072

VL - 104

SP - 1023

EP - 1028

JO - Experimental Physiology

JF - Experimental Physiology

SN - 0958-0670

IS - 7

ER -