Multiple Actions of Rotenone, an Inhibitor of Mitochondrial Respiratory Chain, on Ionic Currents and Miniature End-Plate Potential in Mouse Hippocampal (mHippoE-14) Neurons

Chin-Wei Huang, Kao-Min Lin, Te-Yu Hung, Yao-Chung Chuang, Sheng-Nan Wu
2018 Cellular Physiology and Biochemistry  
Background/Aims: Rotenone (Rot) is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored. Methods: With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated. Results: Addition of Rot produced an inhibitory action on the peak amplitude of I Na with an IC 50 value of 39.3 µM;
more » ... ue of 39.3 µM; however, neither activation nor inactivation kinetics of I Na was changed during cell exposure to this compound. Addition of Rot produced little or no modifications in the steady-state inactivation curve of I Na . Rot increased the amplitude of Ca 2+ -activated Clcurrent in response to membrane depolarization with an EC 50 value of 35.4 µM; further addition of niflumic acid reversed Rot-mediated stimulation of this current. Moreover, when these cells were exposed to 10 µM Rot, a specific population of ATPsensitive K + channels with a single-channel conductance of 18.1 pS was measured, despite its inability to alter single-channel conductance. Under current clamp condition, the frequency of miniature end-plate potentials in mHippoE-14 cells was significantly raised in the presence of Rot (10 µM) with no changes in their amplitude and time course of rise and decay. In simulated model of hippocampal neurons incorporated with chemical autaptic connection, increased autaptic strength to mimic the action of Rot was noted to change the bursting pattern with
doi:10.1159/000489810 pmid:29768258 fatcat:6qykn3cc5bdjfjb6gowgzahuxe