SUBBLOCKING CONCENTRATIONS OF LOCAL-ANESTHETICS - EFFECTS ON IMPULSE GENERATION AND CONDUCTION IN SINGLE MYELINATED SCIATIC-NERVE AXONS IN FROG

Phenomena seen in axons exposed to subblocking doses serve as the basi s for interpreting clinical and behavioral observations during onset a nd recovery of peripheral nerve block. To delineate the changes in exc itability and in impulse conduction caused by subblocking concentratio ns of local anesthetics (LAs) in myelinated peripheral nerve fibers, L As were applied to excised frog sciatic nerves while impulse conductio n was monitored in single axons. For concentrations ranging from 0.01 to 1.2 times the LA concentration needed to block impulse conduction, three measures of susceptibility to LA were made to quantify the actio n of the drugs on ''resting'' fibers (firing rates less-than-or-equal- to 0.5 Hz): the increase in the threshold for electrical activation of impulses, the increase in conduction latency reflecting the slowing o f impulse conduction in the region exposed to LA, and the ''critical b locking concentration'' of LA just sufficient to prevent impulse condu ction in the recorded fiber. Wide interfiber variation in these variab les was observed (e.g., for lidocaine, latency increases at block rang ed from 66% to 257% of control, blocking concentrations ranged from 0. 29 to 1.40 mM), which was not correlated with fiber diameter (as indic ated by resting conduction velocity). Mathematical modeling of impulse conduction in fibers exposed to LA demonstrated that the interfiber v ariation in susceptibility to LA block could result from interfiber di fferences in the density of sodium and potassium channels. The effects of LA were also studied in active fibers (firing rates >0.5 Hz). Loca l anesthetics reversibly inhibited two normally occurring afteroscilla tions in membrane threshold related to afterpotentials following an im pulse. These were ''superexcitability,'' a transient lowering of thres hold lasting as long as 1 s, and ''depression,'' a phase of raised thr eshold peaking within 2-4 s after an impulse and recovering slowly ove r several minutes. Impulse activity also transiently increased the app arent potency of LAs. Such ''use-dependent'' increases in threshold an d decreases in conduction velocity showed kinetics that were agent spe cific, lasting 1 s after a burst of impulses for lidocaine and lasting >10 s for bupivacaine. At low concentrations, within the range of non toxic plasma concentrations after systemic administration, the predomi nant actions of LAs on conducting fibers were transient decreases in e xcitability and conduction velocity in combination with a reduction of intrinsic oscillatory aftereffects of impulse discharge. These effect s may degrade decoding of information in discharge patterns without ac tually blocking conduction of infrequent impulses, suggesting how func tional blockade of coordinated movement and perception may occur even without complete blockade of impulse conduction.