alexa Propafenone preferentially blocks the rapidly activating component of delayed rectifier K+ current in guinea pig ventricular myocytes. Voltage-independent and time-dependent block of the slowly activating component.
Medicine

Medicine

Anatomy & Physiology: Current Research

Author(s): Delpn E, Valenzuela C, Prez O, Casis O, Tamargo J

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Abstract 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.
This article was published in Circ Res and referenced in Anatomy & Physiology: Current Research

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