ESTIMATION OF OUTWARD CURRENTS IN ISOLATED HUMAN ATRIAL MYOCYTES USING INACTIVATION TIME-COURSE ANALYSIS

The aim was to investigate outward currents in single, isolated, human , atrial myocytes and to determine the relative contribution of indivi dual current components to the total outward current. Currents were re corded using the whole-cell patch-clamp technique at 36-37 degrees C. Individual outward current components were estimated from recordings o f total outward current using a mathematical procedure based on the in activation time course of the respective currents. This method allows estimation of outward currents without the use of drugs or conditionin g voltage-clamp protocols to suppress individual current components. A rapidly activating and partially inactivating total outward current w as recorded when myocytes were voltage clamped at potentials positive to -20 mV (peak current density 24.0+/-0.97 pA/pF at +40 mV; n=107 cel ls, 33 patients). This total outward current comprised three overlappi ng currents: a rapidly inactivating, transient, outward current (I-tol ) a slowly and partially inactivating current (ultrarapid delayed rect ifier, I-Kur) and a third current component which most probably reflec ts a non selective cation current (not characterized). The average cur rent densities at +40 mV were 8.92+/-0.44 pA/pF for I-tol and 15.1+/-0 .72 pA/pF for I-Kur (n=107 cells). Recovery from inactivation was bi-e xponential for both currents and was faster for I-tol. A slowly activa ting delayed rectifier current (I-K) was not found. The current densit ies of peak I-tol and I-Kur varied strongly between individual myocyte s, even in those from the same patient. The ratio I-Kur/I-tol was 0.5- 6.9 with a mean of 1.98+/-0.11 (n=107 cells), suggesting that I-Kur is the main repolarizing current. The amplitudes of the total outward cu rrent, I-tol and I-Kur, and the ratio of the latter two were independe nt of patient age (16-87 years).