Being there: cellular targeting of voltage-gated sodium channels in the heart

Voltage-gated sodium (Na(v)) channels in cardiomyocytes are localized in specialized membrane domains that optimize their functions in propagating action potentials across cell junctions and in stimulating voltage-gated calcium channels located in T tubules. Mutation of the ankyrin-binding site of Na(v)1.5, the principal Na(v) channel in the heart, was previously known to cause cardiac arrhythmia and the retention of Na(v)1.5 in an intracellular compartment in cardiomyocytes. Conclusive evidence is now provided that direct interaction between Na(v)1.5 and ankyrin-G is necessary for the expression of Na(v)1.5 at the cardiomyocyte cell surface.