Objective: The purpose of this study was to investigate the properties of the slow component of the delayed rectifier potassium current (I-Ks) in myocytes isolated from undiseased human left ventricles. Methods: The whole-cell configuration of the patch-clamp technique was applied in 58 left ventricular myocytes from 15 hearts at 37 degreesC. Nisoldipine (1 muM) was used to block inward calcium current (I-Ca) and E-4031 (1-5 muM) was applied to inhibit the rapid component of the delayed rectifier potassium current (I-Ks). Results: In 31 myocytes an E-4031 insensitive, but L-735,821 and chromanol 293B sensitive, tail current was identified which was attributed to the slow component of I-K (I-Ks). Activation of I-Ks was slow (tau = 903 +/- 101 ms at 50 mV, n = 24), but deactivation of the current was relatively rapid ( tau =122.4 +/- 11.7 ms at -40 mV, n = 19). The activation of I-Ks was voltage independent but its deactivation showed clear voltage dependence. The deactivation was faster at negative voltages (about 100 ms at -50 mV) and slower at depolarized potentials (about 300 ms at 0 mV). In six cells, the reversal potential was -81.6 +/- 2.8 mV on an average which is close to the K+ equilibrium potential suggesting K+ as the main charge carrier. Conclusion: In undiseased human ventricular myocytes, I-Ks exhibits slow activation and fast deactivation kinetics. Therefore, in humans I-Ks differs from that reported in guinea pig, and it best resembles I-Ks described in dog and rabbit ventricular myocytes
