Harley T Kurata
Pharmacology
University of Alberta
Canada
Biography
Harley T Kurata is a professor belongs to the department of Pharmacology from the university of Alberta.
Research Interest
Ion channel function and modulation in human disease Ion channels are an essential class of proteins that underlie rapid signaling, sensation, and movement in our bodies. These proteins form pores in cell membranes that allow charged ions to pass through and create tiny electrical currents that control cellular activity. Our research program investigates how changes in the function of certain ion channels can lead to diseases, or be targeted to treat certain diseases. Theme 1: Modulation of voltage-gated potassium channels in epilepsy Epilepsy is a diverse collection of neurological disorders characterized by abnormal electrical activity in the brain leading to seizures. An estimated 50 million people worldwide are affected by some form of epilepsy, and startlingly, 30% of affected individuals are resistant to conventional treatments. We are investigating the detailed mechanism of action of a new class of anti-epileptic drug. Retigabine is the prototypical member of this class, and over the past few years has been approved for use in humans in Europe and North America. Retigabine has a unique mechanism of action : it is the only anti-epileptic drug that activates voltage-gated K+ channels in the brain. The molecular target of retigabine (KCNQ channels, or ‘M’-channels) provide an interesting system to investigate ion channel function and pharmacology, and are an important target for the development of new anti-epileptic drugs. We are also investigating a poorly understood mechanism of ‘use-dependent activation’ of Kv1.2-containing neuronal potassium channels. This mechanism allows potassium channels to adapt their behavior in response to repetitive stimulation, and may influence how neurons respond to extreme electrical activity during a seizure. Interestingly, mutations in the Kv1.2 potassium channel gene have been linked to severe epileptic encephalopathy, highlighting the essential role of this channel in the regulation of electrical activity. Theme 2: Genetic forms of diabetes caused by altered electrical activity of pancreatic β-cells. Appropriate release of insulin in response to ingestion of a meal is also controlled by ion channels. In pancreatic β-cells, an important ion channel class named KATP (because they are regulated by intracellular ATP:ADP) control cellular excitability in response to changes in the metabolic state. Mutations in these channels can lead to inheritable forms of diabetes (too little insulin secretion) or hyperinsulinism (too much insulin secretion). We investigate the function and regulation of KATP channels and the effects of commonly used anti-diabetic drugs on these channels.
Publications
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Wrobel E, Rothenberg I, Krisp C, Hundt F, Fraenzel B, Eckey K, Linders JT, Gallacher DJ, Towart R, Pott L, Pusch M, Yang T, Roden DM, Kurata HT, Schulze-Bahr E, Strutz-Seebohm N, Wolters D, Seebohm G. (2016) KCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting. Nat Commun. 7:12795. PMID: 27731317