Method for distinguishing between drug action on impulse propagation versus impulse generation.

Systemic or regional application of local anaesthetics or tetrodotoxin eliminate repetitive impulse discharge, but do they do so by blocking impulse propagation or by suppressing impulse initiation? A method is described for making this distinction based on differences in the pattern of discharge change during the onset of the block. Suppression of conductances involved in downstream impulse propagation produces integer multiplication of the fundamental interspike interval (interspike interval (ISI) doubling, tripling, etc.) In contrast, progressive block of conductances responsible for either the creation of the generator potential, or for its encoding into a spike train, causes a smooth increase in the rhythmic ISI. These two patterns of block, predicted on the basis of fundamental principles and numerical simulations, were verified in in vivo single-axon recordings.