Facile formation of heteromultimeric potassium channels by expression of cloned human cDNAs

Complementary DNAs representing three voltage-gated potassium channels of human origin have previously been expressed in Xenopus laevis oocytes by injecting RNA transcribed in vitro [Ramaswami, M., Gautam, M., Kamb, A., Rudy, B., Tanouye, M. A. & Mathew, M. K. (1990) Mol. Cell. Nueorsci 1, 214-223]. We have coinjected RNAs for pairs of K(+)-channel genes into Xenopus oocytes. Analysis of the kinetics of the evoked currents, their voltage dependence and pharmacological sensitivities demonstrate that channels formed on coinjection of RNA pairs have properties distinct from those evoked by either channel type alone. We conclude that these currents arise from heteromultimeric aggregates of the subunits encoded by the individual RNAs. Quantitative analysis of the currents indicate that at least 60% of the current seen can be ascribed to heteromultimeric channels demonstrating their facile formation. Given that there are a large number of primary transcripts present in the nervous system, the demonstration of pharmacologically distinct heteromultimers may complicate the extension of studies on single, cloned K(+)-channels in heterologous systems to neuronal cells.