Evidence for dimerization of dimers in K+ channel assembly

Voltage-gated Kt channels are tetrameric, but how the four subunits assembl e is not known. We analyzed inactivation kinetics and peak current levels e licited for a variety of wild-type and mutant Kv1.3 subunits, expressed sin gly, in combination, and as tandem constructs, to show that 1) the dominant -pathway involves a dimerization of dimers, and 2) dimer-dimer interaction may-involve interaction sites that differ from those involved in monomer-mo nomer association. Moreover, using nondenaturing gel electrophoresis, we de tected dimers and tetramers, but not trimers, in the translation reaction o f Kv1.3 monomers.