Cytoskeletal interactions determine the electrophysiological properties ofhuman EAG potassium channels

The electrophysiological properties of ether a go-go (EAG) potassium channe ls are modified during the cell cycle when they are expressed in heterologo us systems. In Chinese hamster ovary (CHO) mammalian somatic cells we found that the cell-cycle-dependent modulation of human EAG (hEAG) channels occu rs during the M phase. This modulation has three components: reduction in c urrent density, increased sensitivity to block by intracellular sodium, and increased selectivity for potassium ions. In this work, these three proper ties have been used to define the mitotic phenotype of EAG currents. The si gnaling pathway leading to such changes of channel properties is unknown. W e tested the hypothesis that cytoskeletal interactions might affect the ele ctrophysiological 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 re sults demonstrate that hEAG channels establish complex interactions with cy toskeletal elements, and that these interactions strongly influence the pro perties of the channels. We also conclude that the electrophysiological cha nges observed during the cell cycle are most likely due to reorganization o f the cytoskeleton during the G2/M transition.