Background Transport across the cell membrane by ion channels and carriers regulate virtually all cellular functions including excitability, contraction, metabolism, vascular function, epithelial transport, hormone release, immune response, cell proliferation and cell death. Thus, knowledge of the properties, regulation and pharmacological sensitivity of transport proteins is of outstanding theoretical and clinical interest. Within the past few years a wide variety of human ion channels and carriers have been cloned and are now amenable to analysis on the molecular level. These channels can be expressed in Xenopus oocytes and studied by two electrode voltage clamp and tracer flux. Own research The group focussing on ion channels and carriers have studied the cardiac K+ channels Isk, HERG, the lymphocyte K+ channel Kv1.3, the epithelial Na+ channel rENaC, the anion channel NaPi1, the renal transporters NaPi2, NaPi3 etc., OCT-1, OCT-2, NaSi, rBAT, as well as the osmolyte transporters SMIT and BGT-1 and amino-acid-transporters EAAT4, SN1 and GLAST. They have identified the basic transport properties, the regulation by intracellular signaling molecules, the impairment of transport function by various toxic materials, the functional characterization of genetic transport defects as well as the sensitivity to pharmaceuticals. Applicability The techniques allow the elucidation of transport function at the molecular level and the functional definition of genetic disease. Beyond that ion channels and carriers are prime targets for the pharmacological treatment of a myriad of disorders. The advantages to test the effect of drugs on human transport molecules expressed in oocytes are obvious: 1. The experiments are done in human transport proteins, ruling out errors from species differences. 2. The experiments allow to avoid animal experimentation. 3. The electrophysiological approach allows the testing of a large number of substances at comparably low costs.
Lab MembershipsLang Lab (Principal Investigator/Director)