Modulations of membrane potential oscillations with drive, calcium overload, ryanodine, and caffeine

The objective of this study is to determine the conditions that generate overdrive excitation and overdrive suppression in canine cardiac Purkinje tissue superfused in vitro. Drive-induced (3 Hz) perturbations in the membrane potential of a calcium overloaded (induced by strophanthidin) Purkinje fiber (from a canine heart) were differently modulated by caffeine and ryanodine. Whereas the postdrive oscillations in the membrane potential Vos (single or multiple oscillations in the diastole of the action potential) and/or spontaneous rate (postdrive suppression or postdrive excitation [PDE]) depended on the concentration of strophanthidin (PDE occurred at 2.5 x 10(-7) M, and Vos were seen variably at several concentrations), caffeine (2-3 mM) in the presence of a lower concentration of strophanthidin (1.25 x 10(-7) M) induced PDE. At these lower concentrations, either drug administered alone only induced Vos. On the contrary, the characteristic effects of ryanodine (10(-8) M) in the presence of strophanthidin (2.5 x 10(-7) M) were either a consistent postdrive suppression immediately or the induction of a pronounced afterdepolarization ([AD] a depolarization following the repolarization of the action potential) whose amplitude decreased with time and suppression. At higher concentrations of ryanodine (10(-5) M-10(-6) M) in a calcium overloaded tissue (strophanthidin, 1.25 x 10(-7) M) overdrive induced a pronounced AD in most cases, with subsequent depolarization and cessation of activity in less than 20 minutes. Ryanodine alone caused suppression of postdrive diastolic potential at lower concentrations (10(-9) M-10(-8) M), a pronounced AD (amplitude diminished with later drives), and suppression at higher concentrations (10(-6) M-10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)