The vagal afferent nerves innervate the visceral organs and convey sensory information from the internal environment to the central nervous system. A better understanding of the mechanisms controlling the activation of vagal afferent neurons bears physiological and pathological significance. Although it is generally believed that the magnitude and the rising rate of membrane depolarization are both critical for the action potential generation, no direct or quantitative evidence has been documented so far for the sensitivity of vagal afferent neuron activation to the rate of depolarization and for its underlying ionic mechanisms. Here, by measuring the response of mouse nodose neurons to the suprathreshold current stimuli of varying rising rates, the slowest depolarization capable of evoking action potentials, the rate-of-depolarization threshold (dV/dtthreshold), was determined and found to be ~20 fold higher in the A-fiber neurons compared to the C-fiber neurons classified based on the capsaicin responsiveness and characteristics of action potential waveforms. Moreover, although the dV/dtthreshold varied substantially among individual neurons it was not different in any one neuron in response to different intensities of current stimuli. Finally, inhibition of low-threshold activated D-type potassium current (IK.D) by α-dendrotoxin or low concentration of 4-aminopyrydine nearly abrogated the sensitivity of action potential generation to the depolarization rate. Thus, the depolarization rate is an important independent factor contributing to the control of action potential discharge, which is particularly effective in the vagal afferent A-fiber neurons. The IK.D channel may regulate the excitability of vagal sensory neurons by setting the dV/dtthreshold for action potential discharge.
Ionic Mechanisms Underlying Autonomous Action Potential Generation in the Somata and Dendrites of GABAergic Substantia Nigra Pars Reticulata Neurons In Vitro