FIGURE 10.
Schematic depiction of KCNQ1 translocation and regulation of IKs current density in ventricular myocytes in response to stress. Under basal conditions, KCNE1 is mainly on the lateral cell surface, whereas KCNQ1 is mainly in a cytosolic compartment, associated with or as part of the junctional SR adjacent to t-tubules/z-lines. The IKs current is mediated by a small fraction of available KCNQ1 channels and KCNE1 subunits that are colocalized/assembled on the cell surface. When myocytes are stressed by [Ca2+]i elevation or oxidative overload, junctional SR is partially fragmented. KCNQ1 vesicles exiting the cytosolic compartment travel to the cell periphery, where KCNQ1 is delivered to the cell surface. This leads to an increase in the IKs current density by increased KCNQ1/KCNE1 colocalization/assembly.