Objective To investigate the effects of BmkTXKβ, a newly purified ' long chain' peptide inhibitor of K+ channels from the Chinese scorpion Buthus martensi Karsch (BmK), on the electrophysiological properties ...Objective To investigate the effects of BmkTXKβ, a newly purified ' long chain' peptide inhibitor of K+ channels from the Chinese scorpion Buthus martensi Karsch (BmK), on the electrophysiological properties of isolated rabbit atrial myocytes.Methods The standard whole-cell patch-clamp technique was used to study the effects of multiple concentrations of BmkTXKp on potassium currents and action potentials.Results BmkTXKp produced concentration-dependent prolongation of action potential duration at 20%, 50%, and 90% repolarization (APD20,50,90) without any use-dependence. Meanwhile, it had no significant effect on RMP, APA, or Vmax(n =9). At a dose of 1 μmol/L, BmkTXKβ decreased lto by 41.4% (n = 10, P<0. 01) at a membrane potential of +50 mV [from (13.63±0.87) pA/pF to (7.98±0.78) pA/pF]. lto was reduced significantly with an IC50 value of 1.82μmol/L (95% confidence interval: 1.47 -2.17 μmol/L), in a clear concentration-dependent manner. BmkTXKp blocked IKS and lKs,tail with an IC50 of 20.15 μmol/L and a 95% confidence interval of 16. 93 -23. 37 μmol/L At a concentration of 10 μmol/L, BmkTXKβ blocked both IKS( mean reduction 37. 3% ±4. 2% , P<0. 01, n=7) and lKs,tall(mean reduction 35. 8% ±4. 1%, P<0. 01, n=7). At 0 mV, 10 μmol/L BmkTXKp inhibited both lKr ( mean reduction 40.5% ±2.6%, P < 0. 01, n=6) and lKr,tail ( mean reduction 42. 3% ±2. 9% , P<0. 01, n =6). Blocking of lKr by BmkTXKβ occurred in a concentration-dependent manner, with an IC50 of 17. 21 μmol/L (95% confidence interval; 14. 76 -19. 66 μmol/L). An absence of effects on IK1 was observed for BmkTXKβ, with no change in reversal-potential (n =6, P>0. 05).Conclusions BmkTXKβexerts direct blocking effects on several potassium channels involved in cardiac repolarization, and has a strong effect on prolonging the repolarization of rabbit cardiomyocytes without reverse frequency dependence. This finding suggests that BmkTXKβ could be a promising class Ⅲ drug for anti-arrhythmic therapy without the risk of proarrhythmia.展开更多
基金the Natural Science Foundation of Hubei Province (No. SJ-971073)
文摘Objective To investigate the effects of BmkTXKβ, a newly purified ' long chain' peptide inhibitor of K+ channels from the Chinese scorpion Buthus martensi Karsch (BmK), on the electrophysiological properties of isolated rabbit atrial myocytes.Methods The standard whole-cell patch-clamp technique was used to study the effects of multiple concentrations of BmkTXKp on potassium currents and action potentials.Results BmkTXKp produced concentration-dependent prolongation of action potential duration at 20%, 50%, and 90% repolarization (APD20,50,90) without any use-dependence. Meanwhile, it had no significant effect on RMP, APA, or Vmax(n =9). At a dose of 1 μmol/L, BmkTXKβ decreased lto by 41.4% (n = 10, P<0. 01) at a membrane potential of +50 mV [from (13.63±0.87) pA/pF to (7.98±0.78) pA/pF]. lto was reduced significantly with an IC50 value of 1.82μmol/L (95% confidence interval: 1.47 -2.17 μmol/L), in a clear concentration-dependent manner. BmkTXKp blocked IKS and lKs,tail with an IC50 of 20.15 μmol/L and a 95% confidence interval of 16. 93 -23. 37 μmol/L At a concentration of 10 μmol/L, BmkTXKβ blocked both IKS( mean reduction 37. 3% ±4. 2% , P<0. 01, n=7) and lKs,tall(mean reduction 35. 8% ±4. 1%, P<0. 01, n=7). At 0 mV, 10 μmol/L BmkTXKp inhibited both lKr ( mean reduction 40.5% ±2.6%, P < 0. 01, n=6) and lKr,tail ( mean reduction 42. 3% ±2. 9% , P<0. 01, n =6). Blocking of lKr by BmkTXKβ occurred in a concentration-dependent manner, with an IC50 of 17. 21 μmol/L (95% confidence interval; 14. 76 -19. 66 μmol/L). An absence of effects on IK1 was observed for BmkTXKβ, with no change in reversal-potential (n =6, P>0. 05).Conclusions BmkTXKβexerts direct blocking effects on several potassium channels involved in cardiac repolarization, and has a strong effect on prolonging the repolarization of rabbit cardiomyocytes without reverse frequency dependence. This finding suggests that BmkTXKβ could be a promising class Ⅲ drug for anti-arrhythmic therapy without the risk of proarrhythmia.
