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 pat tern of discharge change during the onset of the block. Suppression of conductances involved in downstream impulse propagation produces inte ger multiplication of the fundamental interspike interval (interspike interval (ISI) doubling, tripling, etc.) In contrast, progressive bloc k of conductances responsible for either the creation of the generator potential, or for its encoding into a spike train, causes a smooth in crease in the rhythmic ISI. These two patterns of block, predicted on the basis of fundamental principles and numerical simulations, were ve rified in in vivo single-axon recordings.