Presynaptic A-current based on heteromultimeric K⁺ channels detected in vivo

Abstract

A WIDE variety of voltage-gated K⁺ channels are involved in the regulation of neuronal excitability and synaptic transmission. Their heterogeneity arises in part from the large number of genes encoding different K⁺ channel subunits (reviewed in ref. 1). In addition, heterologous expression studies indicate that assembly of distinct subunits into heteromultimeric channels may contribute further to K⁺ channel diversity^2–6. A question has been whether heteromeric K⁺ channels actually form in vivo, and if so, whether specific combinations of subunits could account for major K⁺ currents identified in neurons. We present here biochemical evidence that Kvl.4 and Kvl.2, two K⁺ channel subunits of the Shaker subfamily, co-assemble in rat brain. The Kvl.4/Kvl.2 hetero-multimer combines features of both parent subunits, resulting in an A-type K⁺ channel⁶. Immunocytochemical evidence suggests that the heteromultimers are localized in axons and nerve terminals. We propose that Kvl.4/Kvl.2 heteromultimers may form the molecular basis of a presynaptic A-type K⁺ channel involved in the regulation of neurotransmitter release.