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Capillary Endothelial Na + , K + , ATPase Transporter Homeostasis and a New Theory for Migraine Pathophysiology
Author(s) -
Harrington Michael G.,
Fonteh Alfred N.,
Arakaki Xianghong,
Cowan Robert P.,
Ecke Laurel E.,
Foster Hailey,
Hühmer Andreas F.,
Biringer Roger G.
Publication year - 2010
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1111/j.1526-4610.2009.01551.x
Subject(s) - cortical spreading depression , migraine , homeostasis , aura , endocrinology , medicine , vasomotor , pathophysiology , cerebrospinal fluid , migraine with aura , extracellular , anesthesia , chemistry , biochemistry
( Headache 2010;50:459‐478) Background.— Cerebrospinal fluid sodium concentration ([Na + ] csf ) increases during migraine, but the cause of the increase is not known. Objective.— Analyze biochemical pathways that influence [Na + ] csf to identify mechanisms that are consistent with migraine. Method.— We reviewed sodium physiology and biochemistry publications for links to migraine and pain. Results.— Increased capillary endothelial cell (CEC) Na + , K + , ‐ATPase transporter (NKAT) activity is probably the primary cause of increased [Na + ] csf . Physiological fluctuations of all NKAT regulators in blood, many known to be involved in migraine, are monitored by receptors on the luminal wall of brain CECs; signals are then transduced to their abluminal NKATs that alter brain extracellular sodium ([Na + ] e ) and potassium ([K + ] e ). Conclusions.— We propose a theoretical mechanism for aura and migraine when NKAT activity shifts outside normal limits: (1) CEC NKAT activity below a lower limit increases [K + ] e , facilitates cortical spreading depression, and causes aura; (2) CEC NKAT activity above an upper limit elevates [Na + ] e , increases neuronal excitability, and causes migraine; (3) migraine‐without‐aura may arise from CEC NKAT over‐activity without requiring a prior decrease in activity and its consequent spreading depression; (4) migraine triggers disturb, and treatments improve, CEC NKAT homeostasis; (5) CEC NKAT‐induced regulation of neural and vasomotor excitability coordinates vascular and neuronal activities, and includes occasional pathology from CEC NKAT‐induced apoptosis or cerebral infarction.