FACILE FORMATION OF HETEROMULTIMERIC POTASSIUM CHANNELS BY EXPRESSIONOF CLONED HUMAN CDNAS

Complementary DNAs representing three voltage-gated potassium channels of human origin have previously been expressed in Xenopus laevis oocy tes by injecting RNA transcribed in vitro [Ramaswami, M., Gautam, M., Kamb, A., Rudy, B., Tanouye, M. A. and Mathew, M. K. (1990) Mel. 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 cu rrents, their voltage dependence and pharmacological sensitivities dem onstrate that channels formed on coinjection of RNA pairs have propert ies distinct from those evoked by either channel type alone. We conclu de that these currents arise from heteromultimeric aggregates of the s ubunits encoded by the individual RNAs. Quantitative analysis of the c urrents indicate that at least 60% of the current seen can be ascribed to heteromultimeric channels demonstrating their facile formation. Gi ven that there are a large number of primary transcripts present in th e nervous system, the demonstration of pharmacologically distinct hete romultimers may complicate the extension of studies on single, cloned K+-channels in heterologous systems to neuronal cells.