ORIGINAL ARTICLE: PDF OnlyBagwell Ervin E.; Serafino, Randolph; Hungerford, Robin T.; Lindenmayer, George E.Journal of Cardiovascular Pharmacology: December 1987 - p 707-715 Free Abstract Summary: The objective of the present study was to determine the time-courses for depression and recovery of calcium-mediated action potentials in canine Purkinje fibers following exposure to dihydropyridine (DHP) calcium channel antagonists and to determine if the reported discrepancy (up to 1,000 ) between I50 values for inducing physiologic effects in isolated tissues and the dissociation constant (Kd) for [3H]nitrendipine binding to membrane sites could be reduced when physiologic measurements were made under experimentally determined steady-state conditions. Changes in dV/dtmax of slow calcium-mediated action potentials (20 mM KCl, 10−6M isoproterenol) were recorded at 10-min intervals during exposure (2–4 h) to nifedipine, nitrendipine, and PY 108–068 (10−9M-4 × 10−8M). Time to steady state was slow, with half-life t values of 40 min (nifedipine), 84 min (nitrendipine), and 81 min (PY 108–068). Steady state I50 values for depressing dV/dtmax were 12.08 (nifedipine), 5.74 (nitrendipine), and 4.88 nM (PY 108–068). In isolated cardiac sarcolemma preparations (37°C), these compounds competed for [3H]nitrendipine binding sites with Ki values of 8.1, 1.3, and 4.9 nM, respectively. These results show that attainment of steady-state depression of calcium channel function can be slow, but that the discrepancy between the physiologic data and the binding data is reduced significantly (<5°) when physiologic measurements are made at steady state and binding studies are performed at 37°C. © Lippincott-Raven Publishers.