Presynaptic currents in mouse motor endings

Abstract

External electrodes were placed under precise visual control on motor endings of the mouse to record electrical activity promoted by nerve stimulation. Three types of wave form were observed in relation to well-defined electrode emplacements: at the transition between myelinated and nonmyelinated parts of the axon, the wave form consists of 2 negative deflections preceded by a small positivity (preterminal response), at the main part of the terminal branches, a 2-component positive wave form (terminal response) was obtained, and electrode positions in a narrow area between the former and the latter yielded triphasic (positive-negative-positive) wave forms (intermediate responses). Since these responses could not be readily interpreted in terms of classical description of membrane currents associated with propagating action potentials, specific channel blocking agents were used to identify wave form components. Bath application of tetraethylammonium or aminopyridines, or, better, a combination of both, suppressed delayed positive deflections of terminal and intermediate responses and the late negative component of preterminal responses. Local iontophoretic drug application showed that K channels are present only at the terminal part of the endings. K+ efflux promotes a local circuit whose sink is located at the preterminal part where it generates the late negative deflection of the preterminal response. Local application of tetrodotoxin suppressed the 1st negative component of preterminal responses but failed to affect electrical activity at the terminal part of the endings. This indicates that Na channels and action potential generation are restricted to the preterminal part. Suppression of K conductance revealed a slow inward current at the terminal part of the endings which could be identified as a Ca current. Ba2+ and Sr2+ could substitute for Ca2+ as inward current carriers. Activation of spatially separated Na channels, on one side, and of K and Ca channels, on the other, generated ionic currents and separated local circuit currents which flow between preterminal and terminal parts (and vice versa). The signals recorded at each point of motor endings correspond to the sum of ionic and passive currents entering (or leaving) the membrane at that point. The results represent a further example of heterogeneity of axonal membrane.