Different types of K+ channel current are generated by different levels of a single mRNA.

A cloned human voltage‐sensitive K+ channel HLK3 which is present in T‐lymphocytes and in the brain was expressed in Xenopus oocytes and after permanent transfection of a human B‐lymphocyte cell line (IM9). Injections of low cRNA concentrations into Xenopus oocytes led to the expression of a transient K+ current, with saturating current‐voltage (I‐V) relationship, which was abolished by repetitive stimulations due to a slow recovery from inactivation. This transient K+ channel current was fully inhibited by 10 nM charybdotoxin. Injection of high concentrations of the same RNA led to a non‐inactivating K+ current, with linear I‐V curve, which did not undergo use‐dependent inactivation and was hardly sensitive to 10 nM charybdotoxin. Intermediate behaviour due to changing proportions of these two types of K+ channel expression were observed at intermediate RNA concentrations. Transient and non‐inactivating K+ currents were also observed by both whole‐cell and single channel patch‐clamp recording from HLK3 transfected IM9 cells. The main conductance of the channel in the two different modes (inactivating and charybdotoxin‐sensitive or non‐inactivating and charybdotoxin‐resistant) is the same (12–14 pS). Destruction of the cytoskeletal elements with cytochalasin D, colchicine or botulinum C2 toxin in oocyte experiments prevented expression of the sustained mode of the K+ channel. The results suggest that the sustained mode obtained at high RNA concentrations corresponds to channel clustering involving cytoskeletal elements. This differential functional expression of K+ channels associated with different levels of mRNA appears as a new important factor to explain the biophysical and pharmacological diversity of voltage‐sensitive K+ channels.