The KATP channel in migraine pathophysiology: a novel therapeutic target for migraine

Al‐Karagholi, Mohammad Al‐Mahdi; Hansen, Jakob Møller; Severinsen, Johanne; Jansen‐Olesen, Inger; Ashina, Messoud

doi:10.1186/s10194-017-0800-8

Cited by 49 publications

(43 citation statements)

References 98 publications

(99 reference statements)

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“…Nevertheless, the possibility of the involvement of other potential channel targets besides A-type channels in the pathophysiology of migraine can not be ruled out. Although further investigation is clearly necessary in rats with ES-induced migraine, emerging evidence suggests that K ATP channels may play a pivotal role in migraine pathogenesis and could be a potential novel therapeutic anti-migraine target [60].…”

Section: Discussionmentioning

confidence: 99%

Electrical stimulation of the superior sagittal sinus suppresses A-type K+ currents and increases P/Q- and T-type Ca2+ currents in rat trigeminal ganglion neurons

Cao

Zhang

et al. 2019

J Headache Pain

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BackgroundMigraine is a debilitating neurological disorder involving abnormal trigeminovascular activation and sensitization. However, the underlying cellular and molecular mechanisms remain unclear.MethodsA rat model of conscious migraine was established through the electrical stimulation (ES) of the dural mater surrounding the superior sagittal sinus. Using patch clamp recording, immunofluorescent labelling, enzyme-linked immunosorbent assays and western blot analysis, we studied the effects of ES on sensory neuronal excitability and elucidated the underlying mechanisms mediated by voltage-gated ion channels.ResultsThe calcitonin gene-related peptide (CGRP) level in the jugular vein blood and the number of CGRP-positive neurons in the trigeminal ganglia (TGs) were significantly increased in rats with ES-induced migraine. The application of ES increased actional potential firing in both small-sized IB4-negative (IB4−) and IB4+ TG neurons. No significant changes in voltage-gated Na+ currents were observed in the ES-treated groups. ES robustly suppressed the transient outward K+ current (IA) in both types of TG neurons, while the delayed rectifier K+ current remained unchanged. Immunoblot analysis revealed that the protein expression of Kv4.3 was significantly decreased in the ES-treated groups, while Kv1.4 remained unaffected. Interestingly, ES increased the P/Q-type and T-type Ca2+ currents in small-sized IB4− TG neurons, while there were no significant changes in the IB4+ subpopulation of neurons.ConclusionThese results suggest that ES decreases the IA in small-sized TG neurons and increases P/Q- and T-type Ca2+ currents in the IB4− subpopulation of TG neurons, which might contribute to neuronal hyperexcitability in a rat model of ES-induced migraine.

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Section: Discussionmentioning

confidence: 99%

Electrical stimulation of the superior sagittal sinus suppresses A-type K+ currents and increases P/Q- and T-type Ca2+ currents in rat trigeminal ganglion neurons

Cao

Zhang

et al. 2019

J Headache Pain

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“…Functional studies of these mutations have shown that they can result in defective regulation of glutamatergic neurotransmission and the excitatory/inhibitory balance in the brain, which lowers the threshold for cortical spreading depression, a wave of cortical depolarization thought to be involved in headache initiation mechanisms (Sutherland and Griffiths, 2017). KATP channels are also connected to several key molecules in migraine pathogenesis, particularly nitric oxide, CGRP, PACAP and PGI2 known to provoke migraine attacks (Al-Karagholi et al, 2017). Human experimental models have demonstrated that the activation of the cAMP and cGMP pathways can trigger headache in healthy volunteers and migraine attacks in migraine sufferers (Ashina et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Contingent negative variation for the periodicity of migraine attacks without aura

Tian

Guo

et al. 2019

Journal of Integrative Neuroscience

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“…13,14 However, neurovascular signaling mechanisms involving the dural vasculature may contribute to the complex pathobiology of migraine, as well as cluster headache. 4,15,16 Vascular smooth muscle potassium channels play a crucial role in the regulation of arterial diameter. Activation of these channels results in membrane potential hyperpolarization promoting a decrease in the activity of voltage-dependent calcium channels (VDCCs) that ultimately leads to decreased intracellular calcium concentration ([Ca 2þ ] i ), smooth muscle relaxation, and vasodilation.…”

Section: Introductionmentioning

confidence: 99%

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

Syed

Koide

Brayden

et al. 2017

J Cereb Blood Flow Metab

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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.

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The KATP channel in migraine pathophysiology: a novel therapeutic target for migraine

Cited by 49 publications

References 98 publications

Electrical stimulation of the superior sagittal sinus suppresses A-type K+ currents and increases P/Q- and T-type Ca2+ currents in rat trigeminal ganglion neurons

Electrical stimulation of the superior sagittal sinus suppresses A-type K+ currents and increases P/Q- and T-type Ca2+ currents in rat trigeminal ganglion neurons

Contingent negative variation for the periodicity of migraine attacks without aura

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

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