Investigation of the Role of KATP and HCN Channels in Migraine Pathogenesis
Investigation of the Role of KATP and HCN Channels in Migraine Pathogenesis
PhD defence by Zixuan Alice Zhuang
Assessment Committee
Associate professor Anders Hougaard, Department of Clinical Medicine, University of Copenhagen (Chairperson)
Professor Dagmar Beier, The Faculty of Health Sciences, Department of Clinical Research, OUH, Research unit of Neurology
Associate professor Cédric Gollion, Department of Neurology, University Hospital of Toulouse
Supervisors
Clinical Professor Messoud Ashina
MD, PhD Mohammad Al-Mahdi Al-Karagholi
Clinical Associate Professor Faisal Mohammad Amin
Department
Department of Clinical Medicine
Graduate Programme
Neuroscience
Place
Building: Building 7, Room: Auditorium C, Valdemar Hansens Vej 6, 2600 Glostrup
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Short description of the thesis
Migraine affects ~14% of the global population, yet the mechanisms initiating migraine pain remain incompletely understood. This thesis investigates how opening of vascular ATP-sensitive potassium (KATP) channels may lead to migraine pain, focusing on two proposed mechanisms: signalling between blood vessels and nearby pain-sensing neurons through vascular changes and altered potassium gradients, and direct neuronal signalling involving hyperpolarisation-activated cyclic nucleotide-gated (HCN) channel activation. Based on two human migraine provocation studies, complemented by animal data, the thesis shows that KATP channel-induced migraine persists despite reversal of cranial vasodilation and HCN channel blockade. These findings implicate potassium-dependent vascular-to-neuronal signalling in migraine pain genesis and support vascular KATP channels as potential therapeutic targets.