| Summary: | Extracellular recordings of the stimulus evoked compound action potential (CAP) from the mouse optic nerve (MON) display a triphasic profile indicative of the presence of three axon sub-populations of discrete conduction velocity (CV) based on axon size. While larger diameter axons are known to increase CV, the MON is a short central nervous system (CNS) tract and an increase in axon diameter would only marginally increase information arrival time. Therefore, we propose that larger diameter axons exist in the MON to facilitate higher information transfer rates and neuronal firing frequency. The largest axons were most resistant to high frequency stimulus, maintaining their profile while those of the second and third peaks fell in amplitude and increased in latency.
The original dogma suggests that this fall in CAP amplitude is due to accumulating extracellular K+ ([K+]o) which is liberated from the axons during the repolarising phase of the action potential. The use of K+-sensitive microelectrodes demonstrated that the CAP amplitude does not begin to fall until [K+]o is >9 mM. However during a 100 Hz stimulation for 2 minutes, [K+]o only accumulated to ~4 mM due to powerful astrocytic buffering. Therefore, we propose that the CAP amplitude does not fall during high frequency firing due to [K+]o, but alternatively accumulating intracellular Na+ ([Na+]i) which enters axons during stimulation. It proves impossible to achieve accurate real-time measurements of [Na+]i in small central axons. Therefore, indirect methods were used through manipulation of the Nernst equation. The first peak was predicted to accumulate the least [Na+]i, reaching 22.3 mM (SD = 13.0) at 100 Hz stimulation, followed by the second peak 44.7 mM (SD = 10.3) and the third peak, which accumulated [Na+]i to the greatest extent, reaching 62.9 mM (SD = 9.5) during stimulation. We propose that the differential manner with which the three CAP peaks accumulate [Na+]i is due to the surface area-to-volume considerations of varying sized axons, as larger diameter axons possess a higher mitochondrial fraction volume as compared to membranous Na+/K+/ATPase pumps. Therefore, they have a greater capacity to extrude [Na+]i following high frequency firing.
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