Inactivation of Native K Channels.

We have experimented with isolated cardiomyocytes of mollusks Helix. During the whole-cell patch-clamp recordings of K+ currents a considerable decrease in amplitude was observed upon repeated voltage steps at 0.96 Hz. For these experiments, ventricular cells were depolarized to identical + 20 mV from a holding potential of - 50 mV. The observed spontaneous inhibition of outward currents persisted in the presence of 4-aminopyridine, tetraethylammonium chloride or E-4031, the selective class III antiarrhythmic agent that blocks HERG channels. Similar tendency was retained when components of currents sensitive to either 4-AP or TEA were mathematically subtracted. Waveforms of currents sensitive to 1 and 10 micromolar concentration of E-4031 were distinct comprising prevailingly those activated during up to 200 ms pulses. The outward current activated by a voltage ramp at 60 mV x s-1 rate revealed an inward rectification around + 20 mV. This feature closely resembles those of the mammalian cardiac delayed rectifier IKr.