Figure 1. Model components required to simulate regulation of K_v11.1 trafficking and gating, and its effects on ventricular cardiomyocyte electrophysiology.

A, The K_v11.1 trafficking model consists of two-states (M: Membrane, S: Sub-membrane) with four rates (ψ: production rate, α: forward trafficking rate, β: internalisation rate, and δ: degradation rate). The temperature (θ), drugs (λ), and extracellular [K⁺] (κ_b and κ_d) parameters are used to scale the ψ, β, and δ rates. B, The Clancy and Rudy (2001) I_Kr Markov model was used to create a temperature-sensitive model of I_Kr gating by shifting the voltage dependence of certain rates (see Table 2) and scaling each rate with their respective Q₁₀ values (Clancy & Rudy, 2001). In particular, α_n, β_n, α₂^’, and μ rates were scaled with Q_10Activation and Q_{10Deactivation}, while α_i and β_i were scaled with Q_{10Inactivation} and Q_10Recovery, respectively. C, The trafficking, temperature, drug, and extracellular [K]⁺ components controlling I_Kr were embedded in the O’Hara-Rudy (ORd) human ventricular action potential model (O’Hara et al., 2011). Adapted from O’Hara et al. (2011) and the nucleus, endoplasmic reticulum (ER), and Golgi complex (GC) were created with BioRender.com.