Small-signal analysis of K+ conduction in squid axons.

The maximum potential displacement that gives a linear K conductance response was determined to be 1 mV (rms) from a voltage-clamp analysis of TTX treated axons. For perturbations below this amplitude the K conductance kinetics are indistinguishable from a first-order rate process. Linearity and order of kinetics were assessed by four types of measurements: (i) the shape of the onset of the potassium current (sigmoidal vs. exponential); (ii) the symmetry of small hyperpolarizing and depolarizing pulses, (iii) wide band admittance, and (iv) harmonic analysis. The simplest interpretation of the results is that the small-signal linear response arises from a first-order gating mechanism, whereas the large-signal conventional voltage-clamp pulse of tens of millivolts evokes nonlinear phenomena. The small-signal results are consistent with the Hodgkin-Huxley description or any other nonlinear model which fits the large signal data and produces a linear first-order response for small perturbations.