Temperature and redox state dependence of native Kv2.1 currents in rat pancreatic β‐cells

In pancreatic β‐cells, voltage‐dependent K + (Kv) channels repolarise glucose‐stimulated action potentials. Kv channels are therefore negative regulators of Ca 2+ entry and insulin secretion. We have recently demonstrated that Kv2.1 mediates the majority of β‐cell voltage‐dependent outward K + current and now investigate the function of native β‐cell Kv2.1 channels at near‐physiological temperatures (32‐35 °C). While β‐cell voltage‐dependent outward K + currents inactivated little at room temperature, both fast‐inactivation (111.5 ± 14.3 ms) and slow‐inactivation (1.21 ± 0.12 s) was observed at 32‐35 °C. Kv2.1 mediates the fast‐inactivating current observed at 32‐35 °C, since it could be selectively ablated by expression of a dominant‐negative Kv2.1 construct (Kv2.1N). The surprising ability of Kv2.1N to selectively remove the fast‐inactivating component, together with its sensitivity to tetraethylammonium (TEA), demonstrate that this component is not mediated by the classically fast‐inactivating and TEA‐resistant channels such as Kv1.4 and 4.2. Increasing the intracellular redox state by elevating the cytosolic NADPH/NADP + ratio from 1/10 to 10/1 increased the rates of both fast‐ and slow‐inactivation. In addition, increasing the intracellular redox state also increased the relative contribution of the fast‐inactivation component from 38.8 ± 2.1 % to 55.9 ± 1.8 %. The present study suggests that, in β‐cells, Kv2.1 channels mediate a fast‐inactivating K + current at physiological temperatures and may be regulated by the metabolic generation of NADPH.