Age-related changes in Purkinje fiber action potentials of adult dogs

To determine the effects of age on electrophysiological properties of Purkinje fibers (PF), we used standard microelectrode techniques to study PF from normal beagles of five age groups: 19.1 +/- 0.8, 63.7 +/- 2.6, 88.3 +/- 1.9, 107.2 +/- 1.6, and 132.3 +/- 4.3 months (mean +/- SE). Maximum diastolic potential (MDP) did not change over this age range. Action potential (AP) amplitude and maximum upstroke velocity of phase 0 (Vmax) attained peak values at 63.7 months and then declined. As age increased there was an increase in phase 1 repolarization, a prolongation in the time to the peak of the plateau, and a decrease in plateau height. AP duration reached a maximum at 63.7 months and thereafter remained unchanged. Fibers were superfused with the slow channel blocker, AHR-2666, and the fast channel blocker, tetrodotoxin (TTX). AHR-2666 had age-related effects on AP duration, phase 1 repolarization, plateau height, and time to the peak of the plateau. There were no age-related changes in TTX effects on phases 0--2. In another series of experiments, Purkinje fibers from dogs 23 +/- 1.2 to 106 +/- 1.4 months old were superfused with a calcium-rich solution in which Na+ was replaced by tetraethylammonium (TEA+). The resultant slow response action potentials, which are calcium dependent, showed an age-related decrease in AP amplitude, Vmax, and time to peak amplitude. When these fibers were superfused with the slow channel blocker, verapamil, there was an age-related effect on AP amplitude. Our studies indicate that in the normal aging heart, major changes occur in repolarization that appear, in the main, to result from change in the slow inward current carried by Ca2+.