PACEMAKER CURRENT I(F) IN ADULT CANINE CARDIAC VENTRICULAR MYOCYTES

1. Single cells enzymatically isolated from canine ventricle and canin e Purkinje fibres were studied with the whole-cell patch clamp techniq ue, and the properties of the pacemaker current, i(f), compared. 2. St eady-state i(f) activation occurred in canine ventricular myocytes at more negative potentials (-120 to -170 mV) than in canine Purkinje cel ls (-80 to -130 mV). 3. Reversal potentials were obtained in various e xtracellular Na+ (140, 79 or 37 mM) and K+ concentrations (25, 9 or 5. 4 mM) to determine the ionic selectivity of i(f) in the ventricle. The results suggest that this current was carried by both sodium and pota ssium ions. 4. The plots of the time constants of i(f) activation agai nst voltage were 'bell shaped' in both canine ventricular and Purkinje myocytes. The curve for the ventricular myocytes was shifted about 30 mV in the negative direction. In both ventricular and Purkinje myocyt es, the fully activated I-V relationship exhibited outward rectificati on in 5.4 mM extracellular K+. 5. Calyculin A (0.5 mu M) increased i(f ) by shifting its activation to more positive potentials in ventricula r myocytes. Protein kinase inhibition by H-7 (200 mu M) or H-8 (100 mu M) reversed the positive voltage shift of i(f) activation. This effec t of calyculin A also occurred when the permeabilized patch was used f or whole-cell recording. 6. These results indicate i(f) is present in ventricular myocytes. If shifted to more positive potentials i(f) coul d play a role in ischaemia-induced ventricular arrhythmias. The negati ve shift of i(f) in the ventricle might play a role in differentiating non-pacing regions of the heart from those regions that pace.