Ion and water transport mechanisms are critically involved in the regulation of cell proliferation and programmed cell death. In Ehrlich ascites tumor cells (EATC) we find, that the volume regulated anion channel (VRAC), the volume sensitive potassium channel TASK-2, and the water channel AQP5 all play essential roles in cell volume control as well as in cell proliferation and programmed cell death (PCD). In NIH3T3 cells there is an additional role for the Ca²⁺ permeable channel TRPC1 probably functionally coupled to Ca²⁺ activated K⁺ channels. The molecular identity of VRAC is undefined and the mechanisms involved in VRAC activation are poorly understood, although several players have been identified. We find e.g that RhoA although not the volume sensor per se is an important upstream modulator of VRAC in NIH3T3 cells. The roles of VRAC in PCD and in cell proliferation were studied by measurement of VRAC currents, Cl^- movements and membrane potential changes during the cell cycle and during apoptotic volume decrease (AVD), and by using a high affinity anion channel inhibitor, the acidic di-aryl-urea NS3728. Moreover, we have cloned and expressed some members of the TMEM16 family of putative anion channels and using miRNA mediated knockdown and over-expression, respectively, we have investigated the possible involvement of the TMEM16 proteins in volume regulation, proliferation and apoptosis. The role of TASK-2 was studied by over-expression of TASK-2 and by inhibitor studies using clofilium. Tyrosin kinases are involved in the RVD response, but the specific mechanism is not known. An eventual tyrosine phosphorylation of TASK-2 during swelling was thus studied after immunoprecipitation of the channel from HEK cell in which we had over-expressed TASK-2. Using western blotting and the phospho-tyrosin antibody PY100 we found, that there is a large biphasic increase in the tyrosine phosphorylation of the TASK-2 channel after hypotonic cell swelling. EATC express mRNA transcript for AQP5, AQP3 and AQP9, with the expression of AQP5 being 50 times higher than the expression of the others. In multidrug resistant EATC we find, that the expression of AQP5 is strongly downregulated. We have generated stable EATC cell lines with constitutive miRNA mediated knockdown (miR-AQP5) or over-expression (AQP5ex) of AQP5, respectively, and studied them with regard to water permeability, cell volume regulation, growth rates and drug-induced PCD.