ACTIVATION AND INACTIVATION KINETICS OF AN E-4031-SENSITIVE CURRENT FROM SINGLE FERRET ATRIAL MYOCYTES

Ferret atrial myocytes can display an E-4031-sensitive current (l(Kr)) that is similar to that previously described for guinea pig cardiac m yocytes. We examined the ferret atrial l(Kr) as the E-4031-sensitive c omponent of current using the amphotericin B perforated patch-clamp te chnique. Steady-state l(Kr) during depolarizing pulses showed characte ristic inward rectification. Activation time constants during a single pulse were voltage dependent, consistent with previous studies. Howev er, for potentials positive to +30 mV, l(Kr) time course became comple x and included a brief transient component. We examined the envelope o f tails of the drug-sensitive current for activation in the range -10 to +50 mV and found that the tail currents for l(Kr) do not activate w ith the same time course as the current during the depolarizing pulse. The activation time course determined from tail currents was relative ly voltage insensitive over the range +30 to +50 mV (n = 5), but was v oltage sensitive for potentials between -10 and +30 mV and appeared to show some sigmoidicity in this range. These data indicate that activa tion of l(Kr) occurs in at least two steps, one voltage sensitive and one voltage insensitive, the latter of which becomes rate limiting at positive potentials. We also examined the rapid time-dependent inactiv ation process that mediates rectification at positive potentials. The time constants for this process were only weakly voltage dependent ove r the range of potentials from -50 to +60 mV. From these data we const ructed a simple linear four-state model that reproduces the general fe atures of ferret l(Kr), including the initial transient at positive po tentials and the apparent discrepancy between the currents during the initial depolarizing pulse and the tail current.