Long-Term Alteration of S-Type Potassium Current and Passive Membrane Properties in Aplysia Sensory Neurons Following Axotomy

Abstract

In many neurons, axotomy triggers long-lasting alterations in excitability as well as regenerative growth. We have investigated mechanisms contributing to the expression of axotomy-induced, long-term hyperexcitability (LTH) of mechanosensory neurons in Aplysia californica. Electrophysiological tests were applied to pleural sensory neurons 5–10 days after unilateral crush of pedal nerves. Two-electrode current-clamp experiments revealed that compared with uninjured sensory neurons on the contralateral side of the body, axotomized sensory neurons consistently displayed alterations of passive membrane properties: notably, increases in input resistance ( R in), membrane time constant (τ), and apparent input capacitance. In some cells, axotomy also depolarized the resting membrane potential (RMP). Axotomized sensory neurons showed a lower incidence of voltage relaxation (“sag”) during prolonged hyperpolarizing pulses and greater depolarizations during long (2 s) but not brief (20 ms) pulses. In addition to a reduction in spike accommodation, axotomized sensory neurons displayed a dramatic decrease in current (rheobase) required to reach spike threshold during long depolarizations. The increase in τ was associated with prolongation of responses to brief current pulses and with a large increase in the latency to spike at rheobase. Two-electrode voltage-clamp revealed an axotomy-induced decrease in a current with two components: a leakage current component and a slowly activating, noninactivating outward current component. Neither component was blocked by agents known to block other K+ currents in these neurons. In contrast to the instantaneous leakage current seen with hyperpolarizing and depolarizing steps, the late component of the axotomy-sensitive outward current showed a relatively steep voltage dependence with pulses to V m > −40 mV. These features match those of the S-type (“serotonin-sensitive”) K+ current, I K,S. The close resemblance of I K,S to a background current mediated by TREK-1 (KCNK2) channels in mammals, raises interesting questions about alterations of this family of channels during axotomy-induced LTH in both Aplysia and mammals. The increase in apparent C in may be a consequence of the extensive sprouting that has been observed in axotomized sensory neurons near their somata, and the decrease in I K,S probably helps to compensate for the decrease in excitability that would otherwise occur as new growth causes both cell volume and C in to increase. In peripheral regions of the sensory neuron, a decrease in I K,S might enhance the safety factor for conduction across regenerating segments that are highly susceptible to conduction block.