Species variants of the I _sK protein: differences in kinetics, voltage dependence, and La³⁺ block of the currents expressed in Xenopus oocytes

Abstract

We have compared the slowly activating K⁺ currents (I _sK) resulting from 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 dependence, kinetics, and sensitivity to external La³⁺. The current/voltage relationships of the human and rat I _sK currents differed significantly, with greater depolarizations required for activation of the human channel. The first 30 s of activation during depolarizations to potentials between −10 and +40 mV was best described by a triexponential function for each of the three species variants. The activation rates were, however, 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 human currents deactivated more rapidly than the rodent currents. The human and the rodent forms of I _sK were also differentially affected by external La³⁺. Low concentrations (10, 50 μM) rapidly and reversibly reduced the magnitude of the mouse and rat currents during a test depolarization and increased the deactivation rates of the tail currents. In contrast, the magnitude and deactivation rates of the human I _sK currents were unaffected by 50 μM La³⁺.