Anti-Arrhythmia Agents ; blood ; pharmacology ; Blood Pressure ; drug effects ; Cell Membrane ; drug effects ; Disopyramide ; blood ; Humans ; Membrane Potentials ; drug effects

Strychnine (Stry.) has been used, as an instrument for studies of experimental epilepsy, though its precise mode of action has remained obscure. One mechanism of action was partially clarified in 1954 ,by the demonstration that subconvulsive doses of Stry. reduce the amplitude of inhibitory postsynaptic potentials (IPSPs) in the cat's spinal motoneurons (MN). Because of the rapid onset of its action and the absence of effects upon monosynaptic excitatory postsynaptic potentials (EPSPs), it was proposed that Stry. competed with some unidentified transmitter for inhibitory receptor sites on the postsynaptic membrane. Electrophoresis of Stry. is known to block the inhibitory effects of glycine, a likely candidate as an inhibitory transmitter on MN in the cat spinal cord. A Stry. resistant inhibition seems to exist not only in the higher portion of the CNS, but also for the spinal MN. Gamma amino butyric acid (GABA) is a candidate for this synaptic transmitter. In Nembutal anesthetized cat, intracellular recording of spinal MN was performed during Stry. induced seizure. To conclude, it can be said that there were no consistant changes in the MN action potential which would reflect an action of Stry. upon MN's membrane properties important to seizure generation. It is still to be resolved whether the increase in polysynaptic EPSP amplitude is due to a Stry. effect upon the membrane properties of excitatory interneurons or to an effect only upon the inhibitory as well as the EPSPs.
Action Potentials/drug effects* ; Animal ; Cats ; Convulsions/chemically induced ; Female ; Male ; Membrane Potentials/drug effects* ; Motor Neurons/drug effects* ; Spinal Cord/drug effects* ; Strychnine/pharmacology*

Anti-Arrhythmia Agents/blood ; Anti-Arrhythmia Agents/*pharmacology ; Blood Pressure/drug effects ; Cell Membrane/drug effects ; Disopyramide/blood ; Membrane Potentials/drug effects

AIMTo learn the electrophysiological interference of levofloxacin (LVFX) to heart in guinea pig.

METHODSHigh, moderate and low doses of LVFX were given to the anesthetic guinea pig via i.p., and QT interval span and corrected QT-interval span in the II leading lines of ECG were recorded and analyzed from 5 min to 360 min after the drug administration. Single ventricular myocytes were obtained and impacted by LVFX solution of different concentrations. Then delayed rectifier potassium currents (I(K)) on single cells were recorded with whole-cell patch clamp technique, and compared with control group(without impact of LVFX).

RESULTS(1) After the administration of LVFX, at the dose of 200 mg/kg. QT-interval span was significantly elongated, and the increasing rate is 19.38% +/- 3.15% (P < 0.05). While at the relatively lower doses of 50 mg/kg and 100 mg/kg, the elongation is of low/no significance (P > 0.05). (2) LVFX inhibited I(K) dose-dependently and time-dependently.

CONCLUSIONLVFX might prolong the QT-interval span by the mechanism of inhibiting I(K), which implies a potential risk in clinical application.

Animals ; Guinea Pigs ; Levofloxacin ; Membrane Potentials ; Myocytes, Cardiac ; drug effects ; physiology ; Ofloxacin ; pharmacology ; Patch-Clamp Techniques

OBJECTIVEto investigate the effect of deoxypodophyllotoxin (DOP) on membrane potential of dorsal unpaired median neurons (DUM, neurons) and its correlation with sodium channel.

METHODSDUM neurons were labeled with DiBAC4(3). Laser scanning confocal microscope was used to monitor the changes of membrane potential at real time on these neurons that were treated with different concentrations of the DOP. The effect of sodium channel blocker tetrodotoxin (TTX) on the changes was also observed.

RESULTSmembrane potential depolarization induced by the DOP peaked at 5 min and became stabilized after 8min. After compared with fluorescence intensity without treatment, the normalized fluorescence intensity was 69.6 ± 3.0, 72.1 ± 2.7, 77.8 ± 3.6, 86.2 ± 3.1 in cells which were treated with 1, 5, 25, 125 micromol/L DOP, respectively. These numbers were significantly lower than those from untreated control cells (P < 0.01). When DUM neurons were co-incubated with 1 micromol/L TTX for 20 min, then treated with 25 micromol/L DOP, the intensity changed to 63.6 ± 5.4, which was similar to that of the control (P > 0.05). This indicated that the effect of DOP could be completely inhibited by TTX.

CONCLUSIONDOP induced membrane depolarization of DUM neurons in the range of 1 approximately 125 micromol/L and the sodium channel should be involved in this process.

Animals ; Cells, Cultured ; Ganglia, Invertebrate ; drug effects ; physiology ; Membrane Potentials ; drug effects ; physiology ; Neurons ; drug effects ; physiology ; Periplaneta ; drug effects ; physiology ; Podophyllotoxin ; analogs & derivatives ; pharmacology ; Sodium Channels ; metabolism

OBJECTIVETo study the mechanism of myricetin inducing the HepG-2 cell line apoptosis.

METHODThe MTT method was employed to study myricetin pharmacodynamics in HepG-2. The light microscope and transmission was used to identify the tumor cell apoptosis in the morphology. The FCM method and the kit of caspase 3, caspase 9 were hired to detect the apoptosis rates, the content of mitochondrial membrane electric potential and the activity of caspase in cancer cells.

RESULTMyricetin significantly inhibits the proliferation and induces the apoptosis of HepG-2 in a dose-dependent manner, which is accompanied with G2/M and S phase arrest. In addition, myricetin also increases the activation of caspase 3,9 and results in a depolarization and delta psi m collapse in a dose-dependent manner.

CONCLUSIONThe molecular pathway of apoptosis of human hepatocellular carcinoma cell lines induced by myricetin might deal with the mitochondria-mediated pathway.

Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; pathology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Flavonoids ; pharmacology ; Flow Cytometry ; Hep G2 Cells ; Humans ; Membrane Potentials ; drug effects

OBJECTIVETo investigate the effect of ketamine on the high-voltage-activated calcium currents (ICa(HVA)) in rat hippocampal neurons.

METHODSNeurons were cultured from Wistar rat hippocampus. ICa(HVA) was recorded using whole-cell patch clamp technique. After application with ketamine at different concentrations (10, 30, 100, 300, and 1000 μmol/L), the effect of ketamine on ICa(HVA) was evaluated.

RESULTSICa(HVA) was inhibited by ketamine in a concentration-dependent manner. Ketamine at 10 μmol/L showed no effect on ICa(HVA). Four concentrations of ketamine (30, 100, 300,and 1000 μmol/L) reduced the peak ICa(HVA) currents by (17.5 ∓ 4.5)%, (25.5 ∓ 6.9)%, (38.5 ∓ 4.1)%, and (42.3 ∓ 4.6)% respectively,with a mean half maximal inhibitory concentration of 68.2 μmol/L and Hill coefficient of 0.47. The maximal activation membrane potential was shifted to (5.3 ∓ 0.8) from (5.4 ∓ 0.9). The half maximal activation membrane potential of inactivation curve was shifted from(-26.7 ∓ 3.9) mV to(-32.8 ∓ 4.2) mV.

CONCLUSIONKetamine can remarkably inhibit calcium currents in the central neurons,which may explain at least partly the action of ketamine on central nervous system.

Animals ; Calcium Channels ; drug effects ; physiology ; Cells, Cultured ; Hippocampus ; drug effects ; physiology ; Ketamine ; pharmacology ; Membrane Potentials ; drug effects ; Neurons ; drug effects ; physiology ; Rats ; Rats, Wistar

In order to study the anti-viral mechanism of extracted ZG from Gardenia, the effect of extracted ZG on Hep-2 cell membrane potential, Na -K+-ATPase activity and membrane fluidity post infected with parainfluenza virus type 1 (PIV-1) was observed. Acetylcholine which was fluorescent labeled with DiBAC4 (3) was taken as positive control to observe the changes of membrane potential and was measured by flow cytometer. The phosphorus determination method and spectrophotometer were used to measure the Na+-K+-ATPase activity of Hep-2 cell membrane post PIV-1 infection. Hep-2 cell membrane phospholipids was labeled with fluorescent NBD-C6-HPC and membrane fluidity was measured by confocal laser scanning microscope. The results demonstated that after PIV-1 infection the Hep-2 cell membrane potential decreased significantly and the membrane was in the state of hyperpolarization, Na+-K+-ATPase activity increased and membrane fluidity decreased significantly. There was no apparent interferring effect of extracted ZG on the changes of membrane potential and Na+-K+-ATPase activity post PIV-1 infection, while membrane fluidity was improved significantly. Acetylcholine improved the state of hyperpolarization. The changes of membrane potential, Na -K+-ATPase activity and membrane fluidity might be the biomechanism of PIV-1 infectoin. The extracted ZG improved membrane fluidity to prevent from PIV-1 infection by protecting the cell membrane, which was probably the mechanism of anti-PIV-1 activity of the extracted ZG, but ZG probably had nothing to do with membrane potential and Na+-K+-ATPase activity.
Acetylcholine ; pharmacology ; Antiviral Agents ; pharmacology ; Cell Line, Tumor ; Cell Membrane ; drug effects ; Gardenia ; chemistry ; Humans ; Membrane Fluidity ; drug effects ; Membrane Potentials ; drug effects ; Parainfluenza Virus 1, Human ; drug effects ; Plant Extracts ; pharmacology ; Sodium-Potassium-Exchanging ATPase ; metabolism

AIMTo investigate the mechanisms of anti-cancer effect of resveratrol (Res), and the effects of Res in cell apoptosis. The role of Res playing in mitochondrial permeability transition pore (PTP) induction was studied.

METHODSMitochondria was prepared from the liver of Wistar rats. The effects of Res on oxygen consumption of isolated mitochondria from rat liver was measured with Clark-type electrode and resulted in respiration control rate (RCR). Mitochondrial swelling affected by Res was assessed spectrophotometrically, through the changes in absorbance at 540 nm. The PTP opening was learned from the results. Membrane potential of mitochondia was measured through fluorescence spectrophotometry.

RESULTSRes was shown to inhibit the respiration and decrease the RCR of mitochondria. Res can promote the PTP opening mediated by Ca2+. Res was shown to promote the increase of mitochondial membrane potential mediated by Ca2+ and loss of mitochondial membrane potential.

CONCLUSIONRes was shown to inhibit mitochondial respiration and induce PTP opening of mitochondria. These may be one of the pathways that Res showed anti-cancer action and induce cells apoptosis.

Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Calcium ; metabolism ; Female ; Ion Channels ; drug effects ; metabolism ; Membrane Potentials ; drug effects ; Mitochondria, Liver ; drug effects ; physiology ; Mitochondrial Membrane Transport Proteins ; Mitochondrial Swelling ; drug effects ; Rats ; Rats, Wistar ; Stilbenes ; pharmacology

AIMTo investigate the effects of bradykinin on voltage-dependent sodium channel currents in rat dorsal root ganglion neurons (DRG).

METHODSWhole-cell patch clamp technique was used to determine sodium channel current.

RESULTSBradykinin at 0.01 - 10.0 micromol/L dose dependently increased the frequency of repetitive firing of DRG. Bradykinin at 0.01 - 10.0 micromol/L dose dependently enhanced the TTX-R sodium current, and had no effect on TTX-S sodium current.

CONCLUSIONMechanism underlying the inflammation induced by bradykinin is related to the TTX-R sodium channel.

Action Potentials ; drug effects ; Animals ; Bradykinin ; pharmacology ; Ganglia, Spinal ; drug effects ; physiology ; Membrane Potentials ; drug effects ; Neurons ; physiology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Sodium Channels ; drug effects ; physiology