Functional characterization of TMEM16 anion channels

Abstract

The family of TMEM16 (or anoctamin) ion channels comprises 10 members that seem to be permeable for anion and activated by intracellular calcium. The best characterized members of this family, TMEM16A and TMEM16B, function as calcium‐activated chloride channels (CaCC) in many physiological processes such as sensory transduction, transepithelial secretion, cardiac and neuronal excitation, fertilization and smooth muscle contraction. Recently, it has been demonstrated that TMEM16A together with TMEM16F/H/J are activated by hypotonic cell swelling (HTS) and might be a part of an epithelial volume‐regulated anion channel (VRAC). To study possible involvement of TMEM16 channels in VRAC function, we examine expression of all TMEM16 genes in cells that display high or low VRAC activity. Quantitative real‐time PCR experiments demonstrated that TMEM16F and TMEM16K mRNA levels were much higher in cells that showed larger VRAC currents. Currents activated by HTS in HEK293 cells were significantly increased when TMEM16F and TMEM16K were overexpressed. However, in contrast to previously published results, TMEM16A did not respond to HTS whereas its CaCC function was not impaired. Further experiments will be performed to identify activation mechanisms and determine permeation properties of TMEM16F/K channels. Supported by Interuniversity Poles of Attraction Program IUAP Nr.3P4/23.