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

Abstract

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 IC₅₀ value 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 Ca²⁺-activated Cl^- current in response to membrane depolarization with an EC₅₀ 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 ATP-sensitive 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 emergence of subthreshold potentials. Conclusions: The Rot effects presented herein might exert a significant action on functional activities of hippocampal neurons occurring in vivo.

Pioglitazone, a PPAR-γ Activator, Stimulates BKCa but Suppresses IKM in Hippocampal Neurons

“…The recording pipettes used had a resistance of 3–5 MΩ as they were immersed in different solutions described above. Patch-clamp recordings were made in whole-cell, cell-attached, or inside-out configuration by means of an RK-400 (Bio-Logic, Claix, France) or Axopatch 200B patch amplifier (Molecular Devices, Sunnyvale, CA, United States) (Huang et al, 2018; Lai et al, 2018). Liquid junctional potential was commonly nulled immediately before establishment of the seal.…”

Sirtuin 1 Regulates Mitochondrial Biogenesis and Provides an Endogenous Neuroprotective Mechanism Against Seizure-Induced Neuronal Cell Death in the Hippocampus Following Status Epilepticus

“…Both animal and clinical studies [8,9,10,11,12,13] have revealed that continuous epileptic seizures can cause the dysfunction of mitochondria, which may act as a critical player in seizure-induced brain damage. It is well understood that prolonged seizures selectively affect Complex I enzyme activity in the mitochondrial respiratory chain, causing excessive oxidative and nitrosative stress, and resulting in neuronal cell injury or death in the hippocampus—which may induce succeeding epileptogenesis [5,12,14]. Consequently, the mitochondria may possess characteristics to determine the fate of neuronal survival after status epilepticus and play a role in therapeutic modification [5,12].…”

Thallium-201 Imaging in Intact Olfactory Sensory Neurons with Reduced Pre-Synaptic Inhibition In Vivo

“…Mechanisms by which intranasal administration of rotenone induced persistent changes in intrinsic excitability of olfactory sensory neurons remain unclear. One possible mechanism is the acute action of rotenone that involves modulation of ion channels through the production of reactive oxygen species [22]. However, in this study, because rotenone administrated to the nasal cavity was washed out in dissection of olfactory epithelium before electrophysiological recordings, such long-lasting inhibition of ion channels by rotenone may be related with plasticity of neuronal excitability (Fig.…”