SPECIES VARIANTS OF THE I-SK PROTEIN - DIFFERENCES IN KINETICS, VOLTAGE-DEPENDENCE, AND LA3-OOCYTES( BLOCK OF THE CURRENTS EXPRESSED IN XENOPUS)

We have compared the slowly activating K+ currents (I-sK) resulting fr om the expression of the human, mouse, or rat I-sK proteins in Xenopus oocytes, utilizing natural, species-dependent sequence variations to initiate structure-function studies of this channel. Differences were found between the human and rodent currents in their voltage dependenc e, kinetics, and sensitivity to external La3+. The current/voltage rel ationships of the human and rat I-sK currents differed significantly, with greater depolarizations required for activation of the human chan nel. The first 30 s of activation during depolarizations to potentials between -10 and +40 mV was best described by a triexponential functio n for each of the three species variants. The activation rates were, h owever, significantly faster for the human current than for either of the rodent forms. Similarly, deactivation kinetics were best described as a biexponential decay for each of the species variants but the hum an currents deactivated more rapidly than the rodent currents. The hum an and the rodent forms of I-sK were also differentially affected by e xternal La3+. Low concentrations (10, 50 mu M) rapidly and reversibly reduced the magnitude of the mouse and rat currents during a test depo larization and increased the deactivation rates of the tail currents. In contrast, the magnitude and deactivation rates of the human I-sK cu rrents were unaffected by 50 mu M La3+.