Genetik und Physiologie von Kalium-Kanälen in der renalen Elektrolyt- und Blutdruckregulation

• Applicant: Professorin Dr. Ute Scholl
• Subject Area: Anatomy and Physiology
• Term: from 2010 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 164257617

Potassium channels play a key role in human electrolyte and blood pressure homeostasis. We have recently described a novel human syndrome, combining early onset Seizures, Sensorineural deafness, Ataxia, Mental retardation and Electrolyte imbalance (SeSAME), and identified KCNJ10 as the causative gene. KCNJ10 encodes the Kir4.1 inward rectifier K+ channel expressed in brain, inner ear and kidney. In the first part of this project, I plan to study the pathophysiology of SeSAME syndrome on a molecular level by assessing the impact of disease causing mutations on channel expression, trafficking and function. Models of increasing complexity (Xenopus oocytes, a renal cell line, an established knockout mouse model) will then be used to examine the role of Kir4.1 in renal electrolyte homeostasis. We hypothesize that Kir4.1 is necessary for basolateral recycling of K+ for the Na+- K+-ATPase in the distal nephron, raising the question of upstream regulators; the renin angiotensin aldosterone system and the WNK (with no lysine = K) kinases regulating renal salt reabsorption and potassium secretion are excellent candidates for such a pathway. In the second part of this proposal, I will study the role of adrenal two-pore background potassium channels in primary aldosteronism, a form of human hypertension.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Richard P. Lifton, Ph.D.