Effect of paeonol on L-type calcium channel in rat ventricular myocytes.

In order to study the possible mechanisms of paeonol on the cardiovascular system, the effect of paeonol on L-type Ca(2+) channel current (I(Ca,L)) was studied in rat ventricular myocytes using the whole cell patch-clamp technique. Exposure to paeonol (approximately 10 to 1000 microm/l) resulted in a concentration-dependent inhibition of peak I(Ca,L), with a half maximum inhibition concentration, IC(50), of 561 microm/l. Paeonol 600 microm/l inhibited I(Ca,L) by 55.3%, shifted the steady state activation and inactivation curve of I(Ca,L) to more positive and negative potentials, respectively, tended to prolong the recovery of I(Ca,L) from inactivation and did not have a use-dependent effect. However, the current-voltage relationship and reversal potential of I(Ca,L) were not altered. These results suggest that the protection by paeonol against myocardial injury is due to its blocking effect on I(Ca,L).

Puerarin blocks transient outward K+ current and delayed rectifier K+ current in mice hippocampal CA1 neurons.

AIM: To study the effects of puerarin (Pue) on IA and IK in mouse hippocampal neurons. METHODS: The whole cell patch clamp techniques were used. RESULTS: Pue reduced the amplitude of IA and IK, in a concentration-dependent, but not rate- or use-dependent manner (IC50 were 461 micromol/L and 215 micromol/L, respectively). Pue (0.5 mmol/L) shifted the steady state activation curves of IA and IK to positive and negative potentials (Vh about 20.6 mV and 28.6 mV) respectively, but inactivation curves of IA were not affected by Pue. CONCLUSION: Pue inhibited IA and IK in mouse hippocampal CA1 neurons and its blocking effect on I(K) was much stronger than on IA.

Effect of tetramethyl pyrazine on L-type calcium channel in rat ventricular myocytes.

To elucidate possible ionic mechanisms of antimyocardial ischemia and antiarrythmia of tetramethyl pyrazine (TP), we studied L-type Ca2+ currents (I(Ca.L)) in adult rat ventricular myocytes using the whole-cell patch-clamp technique. The results showed: (i) under physiological conditions, 0.25 mmol/L TP decreased amplitude of I(Ca.L) to 60.6% and this inhibition was increased with increasing concentration of TP. ID50 was 0.20 mmol/L. (ii) The Ca2+-antagonistic effect of TP was voltage-dependent. A marked negative shift of the steady-state inactivation curve was observed with long (10 s) conditioning prepulses, but not with short (350 ms) ones. (iii) The time course of inhibition during TP treatment was increased with an increase in drug concentration, and recovery from TP-induced inactivation of I(Ca.L) was slower than in control cases. (iv) Tonic block and use-dependent block with TP treatment, which was induced by increasing the frequency of stimulation, occurred. We suggest that TP inhibits the I(Ca.L) mainly by binding to inactivated Ca2+ channels. The high affinity of TP for the inactivated state of I(Ca.L) may play an important role in developing therapies for pathological conditions.

Calcium-activated potassium current in single Novikoff cell.

The electrophysiological properties of the hemichannels of the gap junction in a single Novikoff cell was studied using patch-clamp whole-cell recording techniques. During the experiments, a transient outward current (peak current, Ip) was found to be evoked by the increment of depolarized pulses. Ip was voltage-dependent and could be inhibited partly by CsCl and tetraethylammonium (TEA), but was blocked completely by quinidine. When the intracellular free Ca2+ concentration ([Ca2+]i) was increased, the amplitude of Ip was enhanced. Adding 10 mmol/l EGTA in the pipette solution, Ip disappeared. When the cells were bathed in symmetrical high-K+ solution, Ip also completely disappeared. These results suggest that Ip is a calcium-activated potassium current, although it cannot be blocked by apamin.

[Bepridil inhibition on the delayed rectifier K+ currents in thyroxine induced hypertrophied guinea pig ventricular myocytes].

AIM: To study the effects of bepridil on the rapidly activating component (IKr), the slowly activating component (IKs) of the delayed rectifier potassium current and the inward rectifier potassium current (IK1) in hypertrophied guinea pig ventricular myocytes. METHODS: The whole cell patch clamp techniques were used. RESULTS: In hypertrophied guinea pig ventricular myocytes, bepridil 30 mumol.L-1 markedly inhibited IKr and IKs (by 20.9% and 27.2% at 0 mV and mV, respectively). The effect of bepridil on IKs was larger than on IKr. Bepridil 30 mumol.L-1 also significantly inhibited the inward component of IK1 (by 15.1% at +100 mV), but the reverse potential of IK1 was unaffected. Bepridil (1-100 mumol.L-1) was shown to inhibit IKr and IKs in a concentration-dependent manner. Their IC50 were 46.7 mumol.L-1 and 23.8 mumol.L-1, respectively. CONCLUSION: Bepridil inhibit IKr, IKs and IK1 in hypertrophied guinea pig ventricular myocytes, which may be important in understanding the antiarrhythmic effects of this drug.

Chronic levothyroxin treatment is associated with ion channel abnormalities in cardiac and neuronal cells.

1. We investigated the ion currents responsible for repolarization of guinea-pig isolated myocytes (ICa) and rat hippocampal CA1 neurons (IA and IK) by means of the whole-cell holding technique. 2. The rat hypertrophied heart, induced by levothyroxin, caused exaggerated cardiac arrhythmias after coronary ischaemia-reperfusion. 3. We found an enhanced ICa in guinea-pig isolated myocytes and decreased IA and IK in rat hippocampal CA1 neurons following levothyroxin treatment. Blockade of the outward K+ current and an increment in inward Ca2+ current by chronic levothyroxin treatment contributed to the delayed repolarization and aggravated cardiac arrhythmias. 4. Animals treated with chronic levothyroxin may serve as pathological models for the investigation of the pattern of ion channel disorders with regard to impaired repolarization and aggravated cardiac arrhythmias.