Temperature Dependence of Bistability in Squid Giant Axons with Alkaline Intracellular pH

Raising the intracellular pH (pHi) above 7.7 in intracellularly perfused squid giant axons causes spontaneous firing of action potentials. The firing frequency ranged from 20 Hz at 0°C to 200 Hz at 23°C. Above 23°C, the axons were quiescent. They were bistable for 13 <T <23°C. That is, they were either quiescent or spontaneously firing. Below 13°C, spontaneous firing was the only stable element. The primary effects of changes in temperature on the underlying ionic currents were on gating of the delayed rectifier potassium channel IK, and the sodium ion channel INa. The kinetics of IK had a Q10 of 3.63. The effect of T on INa was more complicated in that the peak INa amplitude increased with T, as demonstrated in earlier reports. This effect, as well as the changes in INa kinetics produced by changes in T, were mimicked in the context of a model of INa gating in which activation and inactivations are coupled. Electrical activity was simulated in a model of the action potential with appropriate temperature-dependent modifications for INa and IK. The model predicts a change from monostability (spontaneous firing) at relatively low temperatures to bistability (quiescence and spontaneous firing) as the temperature is raised, followed by change back to monostability (quiescence) as the temperature is further increased, which is consistent with the experimental results.