New roles for renal potassium channels.
The role of the kidney in controlling and maintaining plasma potassium levels in the normal range requires the presence and activity of renal potassium channels, and their importance has been highlighted in patients with Bartter syndrome harboring mutations in the ROMK (Kir1.1, KCJN1) channel and hyperkalemia. However, the kidney expresses far more potassium channels than ROMK. Their functions are slowly emerging from studies in animal models and human rare inherited disorders that allow a better understanding of the plethora of functions that potassium channels fulfill in the kidney. Three recent studies shed light on the function of 2 members of the family of voltage-gated potassium channels. The group of René Bindels demonstrates that patients with isolated hypomagnesemia and inappropriately normal magnesuria carry mutations in the Kv1.1 (KCNA) potassium channel (Glaudemans B, et al. J Clin Invest. 2009;119:936-942). Two other studies elucidate a rather complex syndrome involving seizures, ataxia, deafness and renal salt loss, and show that mutations in the Kir4.1 (KCNJ10) potassium channel are responsible (Scholl UI, et al. Proc Natl Acad Sci U S A. 2009;106:5842-5847; Bockenhauer D, et al. N Engl J Med. 2009;360:1960-1970). This human disease is recapitulated by a mouse model deficient for the Kir4.1 channel presenting with similar symptoms. These studies together show that potassium channels in the kidney serve purposes far beyond controlling systemic potassium homeostasis, and are involved in various essential functions of the kidney. Moreover, defects of 2 different potassium channels expressed on opposing membrane domains of the same cells cause distinct symptoms.
Wagner
Carsten A
CA
Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. Wagnerca@access.uzh.ch
D000818:Animals; D001477:Bartter Syndrome / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D053579:Gitelman Syndrome / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007686:Kidney Tubules, Distal / Q000502:physiology*; D051662:Kv1.1 Potassium Channel / Q000235:genetics / Q000502:physiology; D009154:Mutation / Q000235:genetics; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000502:physiology; D000098854:Kcnj10 Channel
D000098854:Kcnj10 Channel; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D051662:Kv1.1 Potassium Channel