Thermodynamically specific gating kinetics of cardiac mammalian K ⁺_(ATP) channels in a physiological environment near 37°C

Abstract

Elementary K⁺ currents through isolated ATP-sensitive K⁺ channels from neonatal rat cardiocytes were recorded to study their temperature dependence between 9°C and 39°C. Elementary current size and, thus, K⁺ permeation through the open pore varied monotonically with temperature with a Q₁₀ of 1.25 corresponding to a low activation energy of 3.9 kcal/mol. Open-state kinetics showed a complicated temperature dependence with Q₁₀ values of up to 2.94. Arrhenius anomalies of τ_open(1) and τ_open(2) indicate the occurrence of thermallyinduced perturbations with a dominating influence on channel portions that are involved in gating but are obviously ineffective in altering pore-forming segments. At 39°C, open-state exit reactions were associated with the highest activation energy (O₂ exit reaction: 12.1 kcal/ mol) and the largest amount of entropy. A transition from 19°C to 9°C elucidated a paradoxical kinetic response, shortening of both O-states, irrespective of the absence or presence of cAMP-dependent phosphorylation. Another member of the K⁺ channel family and also a constituent of neonatal rat cardiocyte membranes, 66 pS outwardly-rectifying channels, was found to react predictably since τ_open increased on cooling. Obviously, cardiac K ⁺_(ATP) channels do not share this exceptional kinetic responsiveness to a temperature transition from 19°C to 9°C with other K⁺ channels and have a unique sensitivity to thermally-induced perturbations.