TMEM16 Proteins Produce Volume-regulated Chloride Currents That Are Reduced in Mice Lacking TMEM16A

Role of volume-regulated and calcium-activated anion channels in cell volume homeostasis, cancer and drug resistance

“…7,9,19 VRAC versus anoctamins The Ca 2C-activated channels ANO1 and ANO6 have been discussed as VRAC candidates. 45 They show outward-rectification and a similar permeability sequence as described for VRAC (SCN ->I ->NO 3 ->Br ->Cl ->gluconate), they are activated by osmotic cell swelling in the presence of extracellular Ca 2C40 and requires cellular ATP. 22,43,44,46 However, VRAC and ANO1/6 activities can be distinguished by (i) their sensitivity to strongly buffered intracellular Ca 2C , i.e.…”

“…78 VRAC is known to play an important role in this process but also ANO proteins appear to play a role in AVD/apoptotic cell death in several cell types investigated. 45,150,151 The amplicon 11q13 contains the Ano1 gene as well as well as a Fas-Associated protein with Death Domain (FADD) gene, i.e., a gene associated with apoptosis, suggesting a coupling between the regulation of ANO1 and cell death. Not much is published about ANO1 and apoptosis.…”

“…55 In 2009, Almaça and coworkers found that anoctamin knockdown significantly reduced the swelling-activated Cl -current and the concommitant RVD in the presence of extracellular Ca 2C . 45 To evaluate the contribution of anoctamins to the RVD response in the presence or absence of extracellular Ca 2C , WT EATC and ANO6-K D EATC (K D Clone: miR-ANO6-1) were exposed to a hypotonic solution and RVD response was followed by electronic cell sizing. In the presence of 0.5 mM extracellular Ca 2C ANO6 K D reduced the rate of RVD (Fig.…”

Role of anoctamins in cancer and apoptosis

“…It was also shown to be activated during cell swelling, probably secondary to an increase in intracellular Ca 2þ [5]. While some detected a role of Ca 2þ -dependent anoctamins, such as Ano1 or Ano6, to volume regulation, others did not [5,6]. Upregulation of endogenous Ca 2þ -activated Cl 2 channels in proliferating cells has been observed recently, but the role of these channels for proliferation has remained unclear [7,8].…”

“…It was also shown to be activated during cell swelling, probably secondary to an increase in intracellular Ca 2þ [5]. While some detected a role of Ca 2þ -dependent anoctamins, such as Ano1 or Ano6, to volume regulation, others did not [5,6].…”