Temperature experiments on nerve and muscle membranes of frogs. Indications for a phase transition

The influence of temperature changes in the range of 25 degrees C to -6 degrees C on the time constants of Na activation (tau m) and inactivation (tau h) was studied in twitch muscle fibers and the node of Ranvier under voltage-clamp conditions. Arrhenius plots of tau m and tau h exhibit a change in activation enthalpy at temperatures below 10 degrees C. Cooling and subsequent heating induce a hysteresis in the temperature dependence of tau m and tau h; Ni2+ and UO22+ increase the hysteresis width. With fast temperature changes the gating kinetics relax to their new values more slowly than the temperature change. Hence, temperature must be changed more slowly than 5 degrees C/min if an additional apparent hysteresis due simply to this relaxation is to be avoided. The data are explained by the hypothesis of a phase transition in the membrane lipids. This conception is favoured over a temperature-induced change in protein conformation, since the neutral local anaesthetic benzocaine shows use-dependent block as if low temperature restricted the access of the drug through the lipid phase to its receptor.