Thermal acclimation modulates membrane proteins as well as their environment, membrane lipids, a known modulator of several membrane proteins. Therefore, the structure-related functional differences in ion channels of thermally acclimated animals can not be tested explicitly without the use of recombinant ion channels expressed in controllable lipid environment. We have compared the functional properties of recombinant and endogenous fish ion channels to separate the regulatory properties mediated via the environment from the protein-structure based differences. We have expressed members of Kir2 family in mammalian cell lines (COS-1 and HEK-293e) and compared their electrophysiological properties and regulation with patch-clamp methods. We have tested channel sensitivity to two conventional blockers, Ba²⁺ and TEA, both of which are thought to interact with only with one – few residues in external part of the ion channel. Surprisingly, both blockers inhibit the potassium current in a cell type dependent manner. For example, trout Kir2 proteins (omKir2.1 & omKir2.2) expressed in COS-1 cells can be blocked with micromolar concentrations of external barium whereas much smaller concentrations are needed to block the channels in fish cardiac myocyte (IC₅₀ from 0.2 to 25 mM). Similar differences exist also in TEA-sensitivity (IC₅₀ from 3 to over 100 mM). Our results demonstrate that a more suitable expression system is needed for the future studies of fish membrane proteins. Beside giving physiologically meaningful results from the isolated teleost membrane proteins the development of an endogenous-like expression system can have interest in membrane – ion channel interactions in general.