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Cytoskeletal interactions determine the electrophysiological properties of human EAG potassium channels

Abstract:

The electrophysiological properties of ether à go-go (EAG) potassium channels are modified during the cell cycle when they are expressed in heterologous systems. In Chinese hamster ovary (CHO) mammalian somatic cells we found that the cell-cycle-dependent modulation of human EAG (hEAG) channels occurs during the M phase. This modulation has three components: reduction in current density, increased sensitivity to block by intracellular sodium, and increased selectivity for potassium ions. In this work, these three properties have been used to define the mitotic phenotype of EAG currents. The signaling pathway leading to such changes of channel properties is unknown. We tested the hypothesis that cytoskeletal interactions might affect the electrophysiological changes observed during the cell cycle. The disruption of actin filaments induces a significant increase in current density, without inducing the cell-cycle-related phenotype. In contrast, disturbance of the microtubules, achieved by pharmacological means or by mechanical excision of the membrane patch, does induce the cell-cycle-related phenotype. Our results demonstrate that hEAG channels establish complex interactions with cytoskeletal elements, and that these interactions strongly influence the properties of the channels. We also conclude that the electrophysiological changes observed during the cell cycle are most likely due to reorganization of the cytoskeleton during the G2/M transition.