Tonic regulation of middle meningeal artery diameter by ATP-sensitive potassium channels

Abstract

Activation of ATP-sensitive potassium (K) channels in arterial smooth muscle (ASM) contributes to vasodilation evoked by a variety of endogenous and exogenous compounds. Although controversial, activation of K channels by neuropeptides such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating peptide (PACAP) in the trigeminovascular system, including the middle meningeal artery (MMA), has been linked to migraine headache. The objective of the current study was to determine if ongoing K channel activity also influences MMA diameter. In the absence of other exogenous compounds, the K channel inhibitors glibenclamide and PNU37883A induced constriction of isolated and pressurized MMAs. In contrast, K channel inhibition did not alter cerebral artery diameter. Consistent with tonic K activity in MMA, glibenclamide also induced ASM membrane potential depolarization and increased cytosolic Ca. Inhibitors of cAMP-dependent protein kinase (PKA) abolished basal K activation in MMA and caused a marked decrease in sensitivity to the synthetic K channel opener, cromakalim. In vivo MMA constriction in response to gibenclamide was observed using two-photon imaging of arterial diameter. Together these results indicate that PKA-mediated tonic K channel activity contributes to the regulation of MMA diameter.

The vascular effect of glibenclamide: A systematic review

“…In contrast, two studies showed that glibenclamide increased the basal tone in rat dural artery including middle meningeal artery. 29,30 Glibenclamide inhibited CGRP-induced dilation in rat basilar and pial arteries. 51,52 However, one study reported that glibenclamide attenuated CGRP-induced dural dilation without affecting CGRP-induced pial dilation.…”

Levcromakalim, an Adenosine Triphosphate‐Sensitive Potassium Channel Opener, Dilates Extracerebral but not Cerebral Arteries

“…Effect of Levcromakalim on Cranial Arteries.-K ATP channels are expressed with different compositions of pore-forming and regulatory subunits which lead to distinct functional properties in different tissue. 19 A recent ultrasonography study demonstrated that levcromakalim caused marked STA dilation with no changes in the velocity of MCA in migraine patients. 29 K ATP channels are expressed in smooth muscle cells and endothelial cells.…”

“…In rats, the activity of K ATP channels contributed to the regulation of MMA diameter and K ATP channel blocker glibenclamide caused a concentration-dependent constriction of isolated MMA, highlight ing the importance of the K ATP channels in the regulation of vascular responses in cranial arteries. 19 A recent ultrasonography study demonstrated that levcromakalim caused marked STA dilation with no changes in the velocity of MCA in migraine patients. 15 In vitro, K ATP channel openers pinacidil, lemakalim, and levcromakalim elicited relaxation of human pial arteries, 31 and the levcromakalim-induced vasodilation was larger in pial arteries compared with extracerebral arteries.…”

“…Particularly, the middle meningeal artery (MMA) is interesting in light of recent data showing that the MMA is the only cranial artery with dilation on the pain side during the early phase of experimentally induced migraine. 19 The effect of K ATP channels on human MMA and its relationship to headache has not been studied. 19 The effect of K ATP channels on human MMA and its relationship to headache has not been studied.…”

“…18 In rats, opening of K ATP channels caused significant MMA dilation. 19 The effect of K ATP channels on human MMA and its relationship to headache has not been studied.…”