Modulation of Axonal Transmission by Metabolic Stress

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Cross, Kevin
computer modeling , metabolic stress , DCMD , locust , Axons , energetics , electrophysiology , persistent sodium
Electrical signaling by neural tissue is responsible for ~20% of the basal metabolic rate. This high-energy consumption predisposes neural tissue to metabolic stress that can compromise signaling and cause irreversible damage. The locust central nervous system (CNS), however, has adaptive mechanisms for surviving metabolic stress and the axon of the descending contralateral movement detector (DCMD) of the locust visual system is capable of modulating high-frequency performance after an anoxic coma to conserve energy. We investigated how other metabolic stresses could modulate the DCMD axon’s performance and what channels are involved in high-frequency signaling that may be a target for metabolic stress. To investigate metabolic stress, we compared azide, a mitochondrial toxin, with starvation of 1- and 4-days. We found azide caused a similar reduction in high-frequency signaling as previously reported after an anoxic coma, reducing conduction velocity (CV) and the number of elicited, high-frequency APs. However, starvation had little effect on the DCMD's performance, and 1-day starvation increased the number of high-frequency APs, suggesting an increase in energy consumption. So, given that after anoxic stress and during azide exposure, high-frequency APs are fewer and conduct slower, we explored mechanisms involved in faithful high-frequency conduction. The DCMD has been previously reported to produce an afterdepolarizing potential (ADP) at high temperatures that could be caused by a T-type calcium channel that may improve high-frequency firing. At high temperatures, we exposed the DCMD axon to cadmium and nickel, both calcium channel blockers, and observed a decrease in CV with a larger effect size for high-frequency APs. Cadmium and nickel exposure also significantly increased the afterhyperpolarization (AHP) that could be caused by blocking T-type calcium channel. However, removal of extracellular calcium failed to confirm the presence of a calcium channel as it did not mimic exposure to divalent cation. Persistent and resurgent sodium channels could also be responsible for the ADP and are known to be blocked by divalent cations. Computer modeling confirmed that a persistent sodium channel could shorten AHP and improve CV. Therefore, we believe persistent sodium channels could be a source of modulation during metabolic stress.
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