4-Aminopyridine causes reduction of cytochromes partly originated in glia with enhanced evoked potentials in the olfactory cortex slice.
Enhanced electrical and metabolic activities with addition of 4-aminopyridine (4-AP) were investigated in the olfactory cortex slice by recording evoked potentials, the redox state of cytochromes and the rate of oxygen uptake. During perfusion with 4-AP (0.01-0.1 mM), the late N-wave was dose-relatedly elicited in the evoked potential, concomitant with reduction of cytochromes and acceleration of oxygen uptake. These enhanced responses by 4-AP (0.1 mM) depended on the extracellular Ca2+. When the slice was subject to 2-deoxy-D-glucose (2-DG) (10 mM), initiation of the late N-wave by 4-AP (0.1 mM) was delayed, and both the reduction of cytochromes and the raised oxygen uptake prompted by the same dose of 4-AP were also significantly attenuated. Nevertheless, the presynaptic potential and N-wave, which markedly diminished by 2-DG, became tolerant to glycopenia after addition of 4-AP. By prior exposure to fluoroacetate (1 mM), the N-wave was gradually increased, but the late N-wave was rapidly decreased in amplitude by adding 4-AP (0.1 mM). The cytochrome reduction and the accelerated oxygen uptake by 4-AP (0.1 mM) were suppressed in the presence of fluoroacetate (1 mM). These results indicate that cytochromes become reduced by 4-AP, concomitant with the enhanced evoked potentials and oxygen uptake in a Ca(2+)-dependent manner, and that glial cells probably contribute to the enhanced electrical and metabolic activities in the olfactory cortex slice.
Saito
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Department of Physiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects*; D003580:Cytochromes / Q000037:antagonists & inhibitors*; D003847:Deoxyglucose / Q000494:pharmacology; D004594:Electrophysiology; D004734:Energy Metabolism / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D005463:Fluoroacetates / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology*; D009830:Olfactory Bulb / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D003580:Cytochromes; D005463:Fluoroacetates; D003847:Deoxyglucose; C014815:fluoroacetic acid; D015761:4-Aminopyridine; D002118:Calcium