1. The Effect And Mechanism Of Rotenone On Delayed Rectifier K⁺ Current (Ⅰ_DR) Of Ventral Mesencephalic Neurons 2. The Expression And Function Of KCNQ Channels In Oligodendrocyte-Lineage Cells(OLCs)

Voltage-gated K+ channels (KV) regulate cell electrical properties, proliferation, migration, and death. Rotenone is a mitochonDRial inhibitor, influencing activity of many channels that potentially participate in cell death processes, but its effect on KV channel in neurons remains unclear. In our present investigation we used whole-cell patch clamp methods and found that extracellular perfusion of rotenone to ventral mesencephalic neuronal cultures caused a significant decrease in delayed rectifier K+ current (IDR) while H2O2 increased it, but had no effect on A-type current (IA) peak amplitude. Meanwhile, both of them enhanced ROS generation. Furthermore, PKA inhibitor H-89 can prevent the decrease in IDR produced by rotenone. Finally, the excitative effect of rotenone on IDR was mimicked by extracellular application of PKA activator foskolin. In summary, our results demonstrate that rotenone acutely decreases IDR channel currents through PKA activation dependent way in ventral mesencephalic neurons. This provided new insights into the mechanism of rotenone-induced neuronal apoptosis. KCNQ genes encode members of the Kv7 family of K+ channel subunits. There are five members of this family– Kv7.1 to Kv7.5; of these, four (Kv7.2–Kv7.5) are expressed in the nervous system. In most neurons native M-channels are composed of Kv7.2 and Kv7.3 subunits or sometimes of homomeric Kv7.2 subunits, although probably with a contribution by Kv7.5 in some neurons; Kv7.4 subunits are predominantly expressed in the auditory and vestibular systems, but also probably contribute to KCNQ channel in central dopaminergic neurons.The main function of KCNQ channel in neurons is control excitability and they can exert a profound dampening effect on repetitive or burst-firing and on the general excitability of neurons. Functional defects of KCNQ channels are linked with many diseases, including epilepsy, cardiac arrhythmias and deafness.Oligodendrocytes are responsible for myelin production in the central nervous system (CNS). They are generated from progenitor cells (OPCs). In vitro, OPCs are often identified by the expression of ganglioside moieties recognized by the A2B5 monoclonal antibody (mAb) and NG2. There are glutamate andγ–aminobutyric acid (GABA) receptors in NG2 cells and the formation of direct synaptic junctions between NG2 cells and glutamatergic and GABAergic neurons. In addition, NG2 positive cells contact with where is unmyelinated. These are implied their role in facilitating the function of neuronal network and these OPCs are capable of receiving and responding to electrical activity in nearby axons. A recent paper examined Na+ currents in cerebellar white matter OPCs cells in rat and the cells can generate anction potention like neurons.Recently, there are several studies of KCNQ channels on neurons, but the expression and function of them in Oligodendrocyte- Lineage Cells (OLCs) remains unclear. In our present investigation, KCNQ2/3/4/5 mRNA and protein were detectable in OPCs, while only KCNQ3/5 mRNA was found in Mature Oligodendrocytes (MOs). KCNQ2/3/5 was merged with MBP very well. There is a discrepancy between RT-PCR and immunocytochemistry date, and these needs further verification.