Figure 8. Temperature-dependent regulation of Kv11.1 gating and trafficking and its effect on ventricular cardiomyocyte repolarization.
A, Time course of changes in Kv11.1 membrane or membrane and sub-membrane levels in response to temperature changes in experiments (symbols) (Zhao et al., 2016; Foo et al., 2019) and model (lines). B, Combined effect of temperature-dependent changes on Kv11.1 gating and trafficking. Higher temperatures acutely increase IKr due to faster gating, but after 24 hours IKr is decreased due to reduced membrane expression of Kv11.1 channels, producing significant prolongation of action potential (AP) duration. C, AP morphology for the first AP after a change in temperature (dashed lines) or after 24 hours (solid lines) at 30, 37, 40, and 41 °C, showing the opposing acute and long-term effects of temperature-dependent regulation of Kv11.1.