Use-dependent block and use-dependent unblock of the delayed rectifier K+ current by almokalant in rabbit ventricular myocytes.

摘要: A voltage-clamp analysis of the effect almokalant on delayed rectifier K+ current (IK) was made in rabbit ventricular myocytes. The two-suction pipette method used, and appropriate protocols were used to study more specifically use dependence, block development, recovery from block. Almokalant interacted with IK two ways: it shifted activation curve hyperpolarizing direction (stimulatory effect) blocked open channel a use-dependent way (inhibitory effect). For 2-second voltage clamps +20 mV, half-maximum obtained at 5 x 10(-8) mol/L, Hill coefficient 1.76. Use-dependent related an open-channel that occurred 0 mV time constant 1.07 second rather slow block: -50 approximately 10 seconds; -75 practically absent. absence important negative membrane potentials is consistent hypothesis drug being trapped channel. limited frequency-dependent could be demonstrated. unblock demonstrated by rapid during stimulation following complete washout drug. It concluded shifts direction, blocks channel, closure gate.