Activation kinetics of the delayed rectifier potassium current of bullfrog sympathetic neurons

We examined the activation kinetics of the delayed rectifier K+ current of bullfrog sympathetic neurons, primarily using whole cell recording. On depolarization, currents activated with a sigmoid delay but did not show a Cole-Moore shift. The time course of activation differed systematically from an exponential raised to a power. At most voltages, a power of 2 gave the best overall fit but a power of 3 better described the initial delay. After the delay, the time course could be fitted by a single exponential. Time constants were 15-20 ms at 0 mV and decreased to a limiting tau = 7 ms at +50 to +100 mV. Tail currents were well fitted by single exponential functions and accelerated with hyperpolarization, from tau = 15-20 ms at 0 mV to tau = 2 ms at -110 mV (e-fold for 40 mV). Eleven kinetic models were evaluated for their ability to describe the activation kinetics of the delayed rectifier. Hodgkin-Huxley-like models did not fit the data well. A linear model where voltage sensor movement is followed by a distinct channel opening step, allosteric models based an the Monod-Wyman-Changeux model, and an unconstrained C-C-C-O model could describe whole cell data from -100 to +40 mV. After including whole cell data at +60 and +80 mV, and a maximal p(open) of 0.8 from noise analysis of cell-attached patches, an allosteric model fit the data best, as the other models had difficulty describing qualitative features of the data. However, some more complex schemes (with additional free parameters) cannot be excluded. We propose the allosteric model as an empirical description of macroscopic ionic currents, and as a model worth considering in future studies on the molecular mechanism of potassium channel gating.