Mechanisms involved in differential conduction of potentials at high frequency in a branching axon.

1. The ionic mechanisms involved in block of conduction of action potentials following high frequency stimulation were studied in a branching axon of the lobster Panulirus penicillatus. 2. A 2-3 mM increase in extracellular K concentration (normal concentration 12 mM) produced block of conduction into both daughter branches. 3. While conduction block induced by high frequency stimulation occurs first into the large daughter branch and only later into the smaller one, propagation into both branches is blocked simultaneously by increased extracellular K concentration. 4. Increasing extracellular K by 2-3 mM resulted in membrane depolarization, reduction in membrane resistance and reduced excitability. The latter two effects were larger than expected from the small depolarization. It appears that increase of extracellular K has direct effects on membrane excitability. 5. It is suggested that block of conduction after high frequency stimulation results from accumulation of K in the extracellular space. However, in order to account for differential conduction block in the two branches one must assume differential buildup of extracellular K concentration around the two branches during high frequency stimulation. 6. Ultrastructural studies using La and horseradish peroxidase as extracellular markers show that the space around the two branches is similar and is open to the extracellular space. Therefore differences in periaxonal volume cannot account for differential buildup of K around the two branches. 7. It is demonstrated that the lobster axon has a Na+/K+ electrogenic pump. After blocking this pump with ouabain, stimulation at high frequency resulted in a conduction block in the two branches almost at the same time. 8. Injection of Ca2+ intracellularly into the thick branch prevents or delays the appearance of conduction block after high frequency stimulation. 9. A mechanism based on these findings is suggested to explain the differential conduction block seen after high frequency stimulation in a branching axon with almost ideal impedance matching.