Electrophysiological properties of mouse and epitope-tagged human cardiac sodium channel Na (v)1.5 expressed in HEK293 cells

Background: The pore-forming subunit of the cardiac sodium channel, Na (v)1.5, has been previously found to be mutated in genetically determined arrhythmias. Na (v)1.5 associates with many proteins that regulate its function and cellular localisation. In order to identify more in situ Na (v)1.5 interacting proteins, genetically-modified mice with a high-affinity epitope in the sequence of Na (v)1.5 can be generated. Methods: In this short study, we (1) compared the biophysical properties of the sodium current (I (Na)) generated by the mouse Na (v)1.5 (mNa (v)1.5) and human Na (v)1.5 (hNa (v)1.5) constructs that were expressed in HEK293 cells, and (2) investigated the possible alterations of the biophysical properties of the human Na (v)1.5 construct that was modified with specific epitopes. Results: The biophysical properties of mNa (v)1.5 were similar to the human homolog. Addition of epitopes either up-stream of the N-terminus of hNa (v)1.5 or in the extracellular loop between the S5 and S6 transmembrane segments of domain 1, significantly decreased the amount of I (Na) and slightly altered its biophysical properties. Adding green fluorescent protein (GFP) to the N-terminus did not modify any of the measured biophysical properties of hNa (v)1.5. Conclusions: These findings have to be taken into account when planning to generate genetically-modified mouse models that harbour specific epitopes in the gene encoding mNa (v)1.5.