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Regulation of Middle Meningeal Artery (MMA) Diameter by ATP‐sensitive potassium channels
Author(s) -
Syed Arsalan,
Koide Masayo,
Brayden Joseph,
Wellman George
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.943.5
Subject(s) - glibenclamide , chemistry , constriction , biophysics , vasodilation , potassium channel , medicine , tonic (physiology) , cerebral arteries , depolarization , endocrinology , anesthesia , biology , diabetes mellitus
The cellular mechanisms contributing to migraine headache are poorly understood, but may involve prolonged dilation of cranial arteries, specifically the MMA. Agonist‐induced activation of ATP‐sensitive potassium (K ATP ) channels is known to play an important role in the modulation of arterial diameter in a number of vascular beds. The objective of the current study was to determine if a tonic vasodilator influence resulting from basal K ATP channel activity is present in isolated, pressurized rat MMA. At an intravascular pressure of 40 mmHg, arteries developed pressure‐induced constriction representing an approximate 40 % decrease in diameter. Treatment of arteries with either of the K ATP channel inhibitors glibenclamide (10 µM) or PNU37883 (10 µM) induced a further decrease in diameter of ∼ 20 %. Also consistent with basal K ATP activity, glibenclamide induced a membrane potential depolarization of ∼ 14 mV in MMA segments at an intravascular pressure of 40 mmHg. Further, in MMA loaded with the ratiometric Ca 2+ indicator, Fura‐2‐AM, glibenclamide‐induced MMA constriction was correlated with a simultaneous increase in the ratio of 340 nm/380 nm excited fura‐2 fluorescence, consistent with an increase in intracellular Ca 2+ . Interestingly, the PKA inhibitor, H89 (1 µM), abolished glibenclamide‐induced MMA constriction suggesting that PKA activity may underlie tonic K ATP channel activation. Glibenclamide or PNU37883 did not alter the diameter of isolated cerebral arteries. Together these results suggest that tonic K ATP channel activity plays a key role in regulation of MMA, but not cerebral artery, diameter and may represent a potential target in the development of treatments for migraine headache.Supported by NIH P01 HL095488, Totman Trust and the Peter Martin Fund.