['The potential pathophysiological role of common SCN5A polymorphisms in cardiac arrhythmias has been increasingly recognized. However, little is known about the impact of those polymorphisms on the pharmocological response of hNav1.5 to various antiarrhythmic agents.', 'The known SCN5A polymorphism, S524Y, was studied in comparison with the wild type (WT) in [corrected] the SCN5A-Q1077del variant. The ion channel gating kinetics and pharmacology were evaluated using whole-cell patch-clamp methods in HEK-293 cells. Consistent with a previous report, the basal ion channel gating kinetics of S524Y were indistinguishable from the WT. Quinidine (20 microM) caused similar extent of tonic block reduction of sodium currents at -120 mV in WT and S524Y. Surprisingly, quinidine (20 microM) exerted a more use-dependent block by a 10 Hz pulse train in S524Y than in WT at 22 degrees C (Ki: WT, 51.3 microM; S524Y, 20.3 microM). S524Y significantly delayed recovery from the use-dependent block, compared with the WT (tau= 88.6 +/- 7.9 s vs 41.9 +/- 6.6 s, P < 0.005). Under more physiological conditions using a 2 Hz pulse train at 37 degrees C, S524Y similarly enhanced the use-dependent block by quinidine. In addition, S524Y enhanced the use-dependent block by flecainide (12.5 microM), but not by mexiletine (100 microM).'] Does a common SCN5A variant alter the responsiveness of human sodium channels to class I antiarrhythmic agents?