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Objective: To study the effect of allitridum on rapidly delayed rectifier potassium current (IKr) in HEK293 cell line., Methods: HEK293 cells were transiently transfected with HERG channel cDNA plasmid pcDNA3.1 via Lipofectamine. Allitridum was added to the extracellular solution by partial perfusion after giga seal at the final concentration of 30 µmol/L. Whole-cell patch clamp technique was used to record the HERG currents and gating kinetics before and after allitridum exposure at room temperature., Results: The amplitude and density of IHERG were both suppressed by allitridum in a voltage-dependent manner. In the presence of allitridum, the peak current of IHERG was reduced from 73.5∓4.3 pA/pF to 42.1∓3.6 pA/pF at the test potential of +50 mV (P<0.01). Allitridum also concentration-dependently decreased the density of the IHERG. The IC50 of allitridum was 34.74 µmol/L with a Hill coefficient of 1.01. Allitridum at 30 µmol/L caused a significant positive shift of the steady-state activation curve of IHERG and a markedly negative shift of the steady-state inactivation of IHERG, and significantly shortened the slow time constants of IHERG deactivation., Conclusion: Allitridum can potently block IHERG in HEK293 cells, which might be the electrophysiological basis for its anti-arrhythmic action.

To investigate the electrophysiology mechanisms of new anxiolytic and antidepressant drug: 4-butyl-alpha-agarofuran (AF-5), patch clamp-recording was used to test the effects of AF-5 on voltage-dependent sodium currents, voltage-dependent potassium currents, L-type voltage-dependent calcium currents and GABA dependent Cl(-) currents in primary cultured rat cortical neurons. Effects of AF-5 on Kv2.1 currents, expressed stably in HEK293 cells, were also tested. Our results showed that, delayed rectifier potassium currents (I(K(DR, L-type voltage-dependent calcium currents (I(LC-ca)) in primary cultured rat cortical neurons and Kv2.1 currents in HEK293 cells were significantly inhibited by AF-5, with IC50 as 6.17, 4.4 and 5.29 micromol x L(-1) respectively. However, voltage-dependent sodium currents (I(Na)), GABA dependent Cl(-) currents and transient outward potassium currents (I(K(A)) in primary cultured rat cortical neurons were not significantly blocked by AF-5. Our results concluded that, blocked I(K(DR)) and I(L-Ca) currents may be one of the mechanisms of anxiolytic and antidepression actions of AF-5.

Objective: Ginkgo biloba extract 50 (GBE50) is a new multicomponent drug with a polyvalent action extracted from the leave of Ginkgo biloba. The aim of this experiment was to study the effects of GBE50 on delayed rectifier potassium current (I(K)) in ventricular myocytes under normal and simulated ischemia conditions in guinea pigs., Methods: Single ventricular myocytes were isolated by an enzymatic dissociation method. I(K) were recorded by whole-cell patch clamp technique in voltage clamp mode. GBE50 was added to the perfusion chamber from low to high concentrations (25, 50,100 mg/L) in normal condition. Different concentrations of GBE50 (25, 50, 100 mg/L) were prepared with simulated ischemic fluid., Results: (1) Under normal condition, 100 mg/L GBE50 decreased I(K) (n = 7, P < 0.05). (2) Under ischemia condition, it was observed that I(K) was inhibited (n = 8, P < 0.05). (3) Perfusion with ischemia solution containing 50 mg/L (n = 8, P > 0.05) and 100 mg/L GBE50 (n = 6, P > 0.05) could reverse the decrease of I(K)., Conclusion: GBE50 significantly decreased I(K) in a concentration-dependent manner. GBE50 could alleviate the electrophysiological heterogeneity of myocardium to prevent ischemic myocardium from arrhythmia.

Aim: To study the effect of Sphingosine-1-phosphate on the delayed rectifier potassium current (IK) and the inward rectifier potassium current (IK1) of guinea pig isolated ventricular myocytes., Methods: Whole cell patch clamp technique was applied to record the delayed rectifier potassium current and the delayed rectifier potassium current of guinea pig isolated ventricular myocytes., Results: (1) IK of S1P (1.1 micromol/L) decreased from (1.2 +/- 0.26)nA to (0.95 +/- 0.23)nA. While IK of S1P (2.2 micromol/L) decreased from (1.43 +/- 0.31)nA to (1.02 +/- 0.28)nA. There was significant difference compared to control group (P < 0.01, n = 6). The IK peak value was decreased from (1.29 +/- 0.26) nA to (1.26 +/- 0.37)nA at the group of S1P (1.1 micromol/L) plus suramin (200 micromol/L) and showed no significant difference compared to control group (P > 0.05, n = 6). (2) IK1 of S1P (1.1 micromol/L) decreased from (-8.94 +/- 2.01)nA to (-8.81 = 1.55)nA. While IK of S1P (2.2 micromol/L) decreased from (-8.86 +/- 1.59)nA to (-8.55 +/- 1.39)nA. There was no significant difference compared to control group (P > 0.05, n = 6)., Conclusion: S1P inhibits delayed rectifier potassium current of ventricular myocyte in guinea pig remarkably, S1P shows no effects on delayed rectifier potassium current of ventricular myocyte in guinea pig.

Objective: To understand what role of the transient outward potassium channels and the delayed rectifier potassium channels play in the mechanism of salicylate-induced tinnitus., Methods: The effects of salicylate on the transient outward potassium channels and the delayed rectifier potassium channels in freshly dissociated inferior colliculus neurons of rats were studied, using the whole-cell voltage clamp method., Results: Salicylate blocked the transient outward potassium current (I(K(A and the delayed rectifier potassium current (I(K(DR in concentration-dependent manner (0.1-1 mmol/L). The IC50 values for the blocking action of salicylate on I(K(A)) and I(K(DR)) were 2.27 and 0.80 mmol/L, respectively. At a concentration of 1 mmol/L, salicylate did not shift the activation and inactivation curves of I(K(A)), but significantly shifted the activation and inactivation curves of I(K(DR)) negatively by approximately 11 mV and 24 mV., Conclusions: Salicylate inhibits both I(K(A)) and I(K(DR)) in rat inferior colliculus neurons but only significantly affects the activation and inactivation kinetics of I(K(DR)). Effects of I(K(A)) and I(K(DR)), especially I(K(DR)), by salicylate may play an important role in salicylate-induced tinnitus.

Aim: To investigate the effect of emodin on the voltage dependent potassium (K(V)) currents in rat proximal colon smooth muscle cells., Methods: Whole cell patch clamp technique was used to record potassium currents including fast transient outward current (I(KA)) and delayed rectifier current (I(Kdr)). Contamination of calcium-dependent potassium currents was minimized with CdCl2 in external solution and EGTA in pipette solution., Results: Emodin (1-30 micromol x L(-1)) reversibly and dose-dependently reduced the amplitude of I(Kdr) with an K(d) value of (1.9 +/- 0.1) micromol x L(-1). I(KA) was also inhibited with 30 micromol x L(-1) emodin to a lesser extent. Although acceleration of the decay rate of the K(V) currents was observed, the block by emodin was not through open block mechanism because a steady state level of inhibition of I(Kdr) was achieved during the first pulse from holding potential -70 mV to + 50 mV after the cells were holding at -70 mV for a three minutes interval in the presence of emodin. Emodin (5 micromol x L(-1)) had no effect on the steady-state activation and inactivation kinetics of K(V) currents, but 30 micromol x L(-1) of emodin produced a positive shift of the voltage dependence of activation, and an increase in the steepness of activation gating as well as shifted the voltage dependence of inactivation to positive direction., Conclusion: Emodin, not through open block mechanism, markedly reduced the amplitude of I(KA) and I(Kdr) and modulated the gating properties of K(V) channels in a reversible and dose-dependent manner.

Aim: To study the effect of ginkgolide B from Ginkgo leave on action potential (AP), L-type calcium current (I(Ca) - L) and delayed rectifier potassium current (I(K)) in normal and ischemic guinea pig ventricular myocytes., Methods: With the standard microelectrode technique to record action potential and whole-cell variant patch-clamp technique to record calcium and potassium current., Results: (1) Under normal condition, ginkgolide B shortened APD and had no effect on RP, AP and V(max). Ginkgolide B also increased I(K) in a concentration dependent manner and had no significant effect on I(Ca) - L (2) Under ischemia condition, it was observed that shortening of APD, APA, decrease V(max) and depolarization of RP was induced by ischemia, but ginkgolide B could attenuate above--mentioned changes. (3) Under ischemia condition, I(Ca) - L and I(K) were inhibited, perfusion with ischemia solution containing ginkgolide B could reverse the decrease of I(Ca) - L and I(K)., Conclusion: Ginkgolide B had protective effect on ischemic myocardium to prevent ischemic arrhythmia.

Aim: The effect of stress hormone corticosterone on hippocampal neurons delayed rectified potassium currents was probed., Methods: The potassium currents of rat hippocampal neurons in primary culture were measured with patch clamp whole-cell recording., Results: It showed that the amplitudes of the potassium currents in hippocampal neurons decreased. However, the threshold potential of potassium currents increased., Conclusion: It is speculated that excessive corticosterone may hurt the hippocampal neurons via its effects on the potassium currents of rat hippocampal cells.