PRESYNAPTIC A-CURRENT BASED ON HETEROMULTIMERIC K-VIVO( CHANNELS DETECTED IN)

A WIDE variety of voltage-gated K+ channels are involved in the regula tion of neuronal excitability and synaptic transmission. Their heterog eneity arises in part from the large number of genes encoding differen t K+ channel subunits (reviewed in ref. 1). In addition, heterologous expression studies indicate that assembly of distinct subunits into he teromultimeric 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 a ccount for major K+ currents identified in neurons. We present here bi ochemical evidence that Kv1.4 and Kv1.2, two K+ channel subunits of th e Shaker subfamily, co-assemble in rat brain. The Kv1.4/Kv1.2 heteromu ltimer combines features of both parent subunits, resulting in an A-ty pe K+ channel6. Immunocytochemical evidence suggests that the heteromu ltimers are localized in axons and nerve terminals. We propose that Kv 1.4/Kv1.2 heteromultimers may form the molecular basis of a presynapti c A-type K+ channel involved in the regulation of neurotransmitter rel ease.