Dantrolene sodium in vitro inhibited the ATP-dependent efflux of calcium from human Fed cells, the Ca++-ATPase activity of red blood cell membrane fragments (RBCMF) and passive calcium binding to RBCMF. These effects were obtained With concentrations of dantrolene sodium between 2.5 and 20 uM. However the passive influx of Ca++ was measured at 37 degrees C in cells pretreated to abolish Ca++ pumping and was not influenced by dantrolene sodium. From these results, it was concluded that dantrolene sodium inhibits an active Ca++ extrusion across the red cell membrane by inhibiting Ca++-ATPase activity which is intimately involved with the Ca++ transport mechanism in the red cell membrane.
Calcium/metabolism* ; Dantrolene/pharmacology* ; Erythrocyte Membrane/drug effects* ; Erythrocyte Membrane/metabolism ; Human ; Ion Channels/drug effects* ; Ion Channels/metabolism

BACKGROUNDShensong Yangxin (SSYX) is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current (I(Na)), L-type calcium current (I(Ca, L)), transient outward potassium current (I(to)), delayed rectifier current (I(K)), and inward rectifier potassium currents (I(K1)) in isolated ventricular myocytes.

METHODSWhole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes.

RESULTSSSYX decreased peak I(Na) by (44.84 +/- 7.65)% from 27.21 +/- 5.35 to 14.88 +/- 2.75 pA/pF (n = 5, P < 0.05). The medicine significantly inhibited the I(Ca, L). At concentrations of 0.25, 0.50, and 1.00 g/100 ml, the peak I(Ca, L) was reduced by (19.22 +/- 1.10)%, (44.82 +/- 6.50)% and (50.69 +/- 5.64)%, respectively (n = 5, all P < 0.05). SSYX lifted the I - V curve of both I(Na) and I(Ca, L) without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of I(to) by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of I(K) was decreased by (30.77 +/- 1.11)% (n = 5, P < 0.05) at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of I(K) was also inhibited. Similar to the effect on I(K), the SSYX inhibited I(K1) by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property.

CONCLUSIONSThe experiments revealed that SSYX could block multiple ion channels such as I(Na) I(Ca, L), I(k), I(to) and I(K1), which may change the action potential duration and contribute to some of its antiarrhythmic effects.

Animals ; Anti-Arrhythmia Agents ; pharmacology ; Calcium Channels ; drug effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Guinea Pigs ; Heart Ventricles ; Ion Channels ; drug effects ; Male ; Myocytes, Cardiac ; drug effects ; Potassium Channels ; drug effects ; Rats ; Sodium Channels ; drug effects

Being a biologic toxin, scorpion toxins have complicate physiologic and pharmalogic actions because of its intricate components. This text reviewed the effect of scorpion toxins on endothelial cell function, platelet function, microcirculation, atherosclerosis, ironic channel, and cardiac function.
Animals ; Endothelial Cells ; metabolism ; Epoprostenol ; metabolism ; Ion Channels ; drug effects ; Microcirculation ; drug effects ; Myocardial Contraction ; drug effects ; Platelet Aggregation ; drug effects ; Scorpion Venoms ; pharmacology ; Tissue Plasminogen Activator ; metabolism

The effects of vanadate on cellular Ca2+ movements across the sarcolemma of cardiac muscle cells were investigated by measuring the intracellular and extracellular Ca2+ activities of guinea pig papillary muscle with Ca2+-selective electrodes. During the rest period following a steady-state of 2 contractions per second the extracellular Ca2+ concentration was increased over the basal level within a minute. During the rest period Ca2+ was transported across the sarcolemma into the extracellular space. Vanadate decreased the change in extracellular Ca2+ concentration during the rest period implying that the Ca2+ efflux across the sarcolemma was decreased by vanadate. Vanadate increased intracellular Ca2+ activities significantly (from 1.9 X 10(-7) M to 10(-6)M) resulting in an increase in resting tension. These results suggest that vanadate decreases Ca2+ efflux from the cells into the extracellular space by blocking Ca2+ transport across the sarcolemma, possibly blocking the Na+-Ca2+ exchange transport.
Animal ; Calcium/metabolism* ; Female ; Guinea Pigs ; Ion Channels/drug effects* ; Male ; Membrane Potentials/drug effects ; Papillary Muscles/drug effects* ; Vanadates ; Vanadium/pharmacology*

OBJECTIVETo study the effects and mechanism of hydrogen peroxide (H2O2) of low concentration on dynamic changes of intracellular free calcium contents ([Ca2+]i) in cultural rat liver oval cells (WB-F344 cells).

METHODSUsing Fluo-3/Am as fluorescent indicator of [Ca2+]i and it was measured by laser scanning confocal microscope system.

RESULTSThe results showed that: (1) A rapid transient spiking of [Ca2+]i occurred after the stimulation of H2O2 of low concentration (800 nmol/L). (2) The [Ca2+]i increase was abolished by pretreated with catalase (CAT) or by incubated in D-Hank's solution containing EGTA, the chelate of extracellular Ca2+. (3) The [Ca2+]i increase was not inhibited by pretreated nifedipine, Ca2+ channel blocker, but was abolished by pretreated with anthracere-9-cardoxylic acid (A9C), the Cl-channel blocker and which also blocked calcium activated non-selective cation channel (CAN).

CONCLUSIONSThese results suggest that the increase of [Ca2+]i induced by H2O2 of low concentration may be due to the influx of extracellular Ca2+ through CAN.

Animals ; Calcium ; metabolism ; Cells, Cultured ; Hepatocytes ; metabolism ; Hydrogen Peroxide ; pharmacology ; Ion Channels ; drug effects ; Microscopy, Confocal ; Rats

Adenosine ; pharmacology ; Animals ; Cyclic Nucleotide-Gated Cation Channels ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Ion Channels ; physiology ; Isoproterenol ; pharmacology ; Membrane Potentials ; drug effects ; Muscle, Smooth, Vascular ; physiology ; Myocytes, Smooth Muscle ; physiology ; Potassium Channels ; Pulmonary Veins ; physiology ; Rabbits

The gating mechanism of ClC-1 chloride channel was studied in this paper by heteroexpression of rat wild type ClC-1 gene in Xenopus oocytes and by two-electrode voltage clamping technique. The deactivation gating kinetic parameters were obtained by applying two exponential fitting of the deactivating currents at various extracellular chloride concentrations. It was found that decrease in extracellular chloride concentration increased the fractional amplitude of fast deactivating component, and depressed the fractional amplitude of slow deactivating component accompanied by a decrease in fast and slow deactivating time constants. These results demonstrate that the deactivation kinetic parameters of ClC-1 are largely dependent on the extracellular chloride concentration, which induces changes in channel gating.
Animals ; Chloride Channels ; drug effects ; physiology ; Chlorides ; pharmacology ; Electrophysiology ; Female ; In Vitro Techniques ; Ion Channel Gating ; drug effects ; physiology ; Oocytes ; physiology ; Rats ; Xenopus

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

Neuropeptide Y (NPY) co-exists with norepinephrine (NE) in sympathetic terminals, and is the most abundant neuropeptide in myocardium. Many studies have focused on the effects of NE on ion channels in cardiac myocytes and its physiological significance has been elucidated relatively profoundly. There have been few investigations, however, on the physiological significance of NPY in myocardium. The effects of NPY on L-type Ca2+ channel currents (I(Ca-L)) were evaluated in some studies and different results were presented, which might be attributed to the different species of animal tested and different methods used. It is necessary, therefore, to study the effects of NPY on ion channels in cardiac myocytes systematically and further to discuss the biological significance of their coexistence with NE in sympathetic terminals. The single ventricular myocytes from adult rat or guinea pig (only for measuring I(K)) were prepared using enzymatic dispersion. I(Ca-L), I(to), I(Na/Ca), I(Na) and I(K) in the cellular membrane were observed using whole cell voltage-clamp recording. In the present study, NPY from 1.0 to 100 nmol/L dose-dependently inhibited I(Ca-L) (P<0.01, n=5). The maximal rate of inhibition in this study reached 39% and IC(50) was 1.86 nmol/L. NPY had no effect on the voltage-dependence of calcium current amplitude and on the voltage-dependence of the steady-state gating variables. I(Ca-L) was activated at -30 mV, reaching the maximum at 0 mV. When both NE and NPY were applied with a concentration ratio of 500:1, 10 nmol/L NPY inhibited I(Ca-L) that had been increased by 5 mumol/L NE, which was consistent with the effect of NPY only on I(Ca-L). NPY also inhibited I(Na/Ca). At a concentration of 10 nmol/L, NPY inhibited inward and outward I(Na/Ca) from (0.27+/-0.11) pA/pF and (0.45+/-0.12) pA/pF to (0.06+/-0.01) pA/pF and (0.27+/-0.09) pA/pF, respectively (P<0.05, n=4). NPY at 10 nmol/L increased I(to) from (12.5+/-0.70) pA/pF to (14.7+/-0.59) pA/pF(P<0.05, n=4). NPY at 10 nmol/L did not affect I(Na) in rat myocytes and I(K) in guinea pig myocytes. NPY increased the speed of action potential depolarization and reduced action potential duration of I(Ca-L), I(Na/Ca) and I(to), which contributed to the reduction of contraction. These results indicate that the effects of NPY are opposite to the effects of NE on ion channels of cardiac myocytes.
Animals ; Calcium Channel Blockers ; pharmacology ; Calcium Channels, L-Type ; drug effects ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; Ion Channels ; drug effects ; Male ; Myocytes, Cardiac ; metabolism ; Neuropeptide Y ; pharmacology ; Norepinephrine ; Patch-Clamp Techniques ; Rats ; Rats, Wistar ; Sodium-Calcium Exchanger ; antagonists & inhibitors

Animals ; Dose-Response Relationship, Drug ; Guinea Pigs ; Heart Ventricles ; Ion Channels ; antagonists & inhibitors ; physiology ; Male ; Myocytes, Cardiac ; drug effects ; physiology ; Promethazine ; pharmacology ; Terfenadine ; pharmacology ; Time Factors