Delpón E, Valenzuela C, Pérez O, Casis O, Tamargo J
Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
Circ Res. 1995 Feb;76(2):223-35. doi: 10.1161/01.res.76.2.223.
The effects of propafenone on the delayed rectifier K+ current were studied in guinea pig ventricular myocytes by using the patch-clamp technique. In these myocytes, this current consists of at least two components: a La(3+)-sensitive component activating rapidly with moderate depolarizations and a La(3+)-resistant current slowly activating at more positive potentials. In the absence of La3+ (when both components are present), propafenone inhibited the delayed outward current, its effects being more marked after weak than after strong depolarizations. Propafenone-induced block of the tail currents elicited on return to -30 mV was more marked after short than after long depolarizing pulses. In the presence of 1 mumol/L propafenone, the envelope-of-tails test was satisfied, thus indicating that at this concentration propafenone completely blocks the rapidly activating component. In the presence of La3+ (when only the slow component is present), the steady state inhibition induced by 5 mumol/L propafenone on both the maximum activated and the tail currents was independent of the test pulse voltage. Development of propafenone-induced block on the slowly activating component was very fast and linked to channel opening. In addition, the blockade appeared to be use dependent, with the rate constant of the onset kinetics at 2 Hz being 0.44 +/- 0.1 pulse-1. The recovery process from propafenone-induced block exhibited a time constant of 2.5 +/- 0.4 s. These results indicated that propafenone preferentially inhibits the rapidly activating component of the delayed rectifier and that it blocks in a voltage-independent and time-dependent manner the slow component of this current.
采用膜片钳技术研究了普罗帕酮对豚鼠心室肌细胞延迟整流钾电流的影响。在这些心肌细胞中，该电流至少由两个成分组成：一个对镧（La³⁺）敏感的成分，在适度去极化时迅速激活；以及一个对La³⁺不敏感的电流，在更正电位时缓慢激活。在没有La³⁺的情况下（此时两个成分均存在），普罗帕酮抑制延迟外向电流，其作用在弱去极化后比强去极化后更明显。回到-30 mV时引发的普罗帕酮诱导的尾电流阻断在短去极化脉冲后比长去极化脉冲后更明显。在存在1 μmol/L普罗帕酮的情况下，满足尾电流包络测试，因此表明在此浓度下普罗帕酮完全阻断快速激活成分。在存在La³⁺的情况下（此时仅存在缓慢成分），5 μmol/L普罗帕酮对最大激活电流和尾电流诱导的稳态抑制与测试脉冲电压无关。普罗帕酮对缓慢激活成分的阻断发展非常迅速，且与通道开放有关。此外，这种阻断似乎具有使用依赖性，在2 Hz时起始动力学的速率常数为0.44±0.1脉冲⁻¹。从普罗帕酮诱导的阻断中恢复的过程表现出2.5±0.4 s的时间常数。这些结果表明，普罗帕酮优先抑制延迟整流器的快速激活成分，并且它以电压无关和时间依赖的方式阻断该电流的缓慢成分。
