Accommodation to hyperpolarization of human axons assessed in the frequency domain

Human axonsin vivowere subjected to subthreshold currents with a threshold-"ZAP" profile (Impedance [ Z: ] A: mplitude P: rofile) to allow the use of frequency domain techniques to determine the propensity for resonant behavior, and to clarify the relative contributions of different ion channels to their low-frequency responsiveness. Twenty-four studies were performed on the motor and sensory axons in 6 subjects. The response to oscillatory currents was tested between 'DC' and 16 Hz. A resonant peak at ~2 to 2.5 Hz was found in the response of hyperpolarized axons, but there was only a small broad response in axons at resting membrane potential (RMP). A mathematical model of axonal excitability developed using DC pulses provided a good fit to the frequency response for human axons, and indicated that the hyperpolarization-activated currentIh, and the slow potassium currentIKsare principally responsible for the resonance. However the results indicate that if axons are hyperpolarized more than -60% of resting threshold, the only conductances that are appreciably active areIhand the leak conductance - i.e., that the activity of these conductances can be studiedin vivovirtually in isolation at hyperpolarized membrane potentials. Given that the leak conductance dampens resonance it is suggested that the -60% hyperpolarization used here is optimal forIh As expected differences between the frequency responses of motor and sensory axons were present and best explained by reduced GKs, up-modulation ofIhand increased persistent Na(+)current,INaP(due to depolarization of RMP) in sensory axons