Many types of rare inherited genetic disorders profoundly affect children and their families. While disorders like Anderson syndrome, Bartter's syndrome, and DEND (Diabetes with Epilepsy and Neuromuscular Defects) affect different organ systems and manifest with different symptoms, these diseases are all caused by genetic mutations in the KIR family of proteins. Mutations in KIR proteins can also be involved in less severe symptoms, including cardiac arrhythmias and vascular defects. The KIR proteins are a family of ion channels known as inwardly rectifying potassium channels. These ion channel proteins form pores in cell membranes, which can be switched on or off, by opening or closing “gates” in the ion-conducting pore. When the gates are open, charged ions can pass across the membrane, generating electrical currents and influencing the membrane voltage. These KIR proteins regulate a diverse set of processes, from beating of the heart to hormone release from the pancreas, and can be influenced by a number of cellular processes and molecules.
Dr. Harley Kurata’s work is focused on the KATP channel, which is a member of the KIR family and is regulated by the “fuel” (ATP) that drives all cells. The KATP channel can sense the metabolic state of cells and serves as a critical trigger for insulin release from pancreatic beta-cells. KATP channel mutations are now recognized as an important cause of genetically inherited insulin disorders, ranging from diabetes (too little insulin released) to hyperinsulinism (too much insulin). Dr. Kurata's team hopes that by identifying the specific mutations involved in KATP, therapeutic approaches to both diseases can be developed. KATP channels are also present in the heart, and although their role in cardiovascular function remains enigmatic and controversial, further investigation of this unique set of proteins has the potential to impact other diseases.