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.