IDENTITY OF A NOVEL DELAYED RECTIFIER CURRENT FROM HUMAN HEART WITH A CLONED K+ CHANNEL CURRENT

In human myocardium, the nature of the K+ currents mediating repolarization of the action potential is still speculative. Delayed rectifier channels have recently been cloned from human myocardium, but it is unclear whether or not these currents are involved in the termination of the cardiac action potential plateau. In intact human atrial myocytes, we have identified a rapid delayed rectifier K+ current with properties and kinetics identical to those expressed by a K+ channel clone (fHK) isolated from human heart and stably incorporated into a human cell line for the first time. The myocyte current amplitude was 3.6+/-0.2 pA/pF (at +20 mV, n=15) and activated with a time constant of 13.1+/-2 milliseconds at 0 mV (n=15). The half-activation potential (V0.5) was -6+/-2.5 mV (n=10) with a slope factor (k) of 8.6+/-2.2 (n=10). The heterologously expressed fHK current amplitude was 136 pA/pF (at +20 mV, n=9) with an activation time constant of 11.8+/-4.6 milliseconds at 0 mV; V0.5 was -4.1+/-2.4 mV (mean+/-SEM, n=8); and k was 7.0. The conductance of single fHK channels was 16.9 picosiemens in 5 mM bath K+. Both native and cloned channel currents inactivated partially during sustained depolarizing pulses. Both currents were blocked by micromolar concentrations of 4-aminopyridine and were relatively insensitive to tetraethylammonium ions and class III antiarrhythmic agents. They had a half blocking concentration (K0.5) for block by 4-aminopyridine of almost-equal-to 50 muM but were relatively resistant to clofilium (K0.5 was 60+/-13 muM, n=6 for fHK). The strong correspondence between the properties of the two currents provides the first demonstration that a specific K+ channel produces a rapid delayed rectifier current in human cardiac tissue.