Mechanisms by Which Calcium Modulates Diastolic Depolarizationin Sheep Cardiac Purkinje Fibers Juan Tamargo, MD,* and Mario Vassalle, MD Abstract: The mechanisms by which calcium modulates diastolic depolariza- tion (DD) in sheep cardiac Purkinje fibers were studied in zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM vitro. Increasing [Cal, from 2.7 mM to 10.8 mM increased both the slope and amplitude ofDD, induced oscillatory potentials (V,,), and prolonged depolarization (V,,). The steepening of DD occurred even in the absence of an obvious V,,. The increase in DD amplitude was due both to an increase in the maximum diastolic potential and to a less negative steady-state level. At constant [Cal,, increasing the driving rate had effects similar to those induced by increasing [Cal,. The increase in DD slope and amplitude was least at the slowest rates and leveled off at the fastest rates in high [Cal,. Lowering [Cal, decreased DD slope and amplitude, but spontaneous activity could be present during interruption of the drive. In slowly driven fibers, increasing [Cal,, to 10.8 mM initially shifted the maximum diastolic potential and steady state DD to more negative values, and subse- quently shifted the latter (but not the former) to less negative values. On re- covery, a transient depolarization occurred. Quiescent fibers exposed to high [Cal, also underwent a transient hyperpolarization and a subsequent depolar- ization, whereas reciprocal effects occurred when [Cal, was lowered. It is con- cluded that [Cal0 modulates DD through several different mechanisms and that most (but not all) modifications induced are brought about by changes in [Cal,. Key words: calcium, rate of discharge, diastolic depolarization, calcium over- load, oscillatory potential, prolonged depolarization. In cardiac Purkinje fibers, the slope of diastolic de- polarization (DD) becomes steeper when the extra- cellular calcium concentration ([Cal,) is increased zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDC From the Department of Physiology, State University of New York, Health Science Center, Brooklyn, New York. *Dr. Tamargo is currently at the Departamento de Farmacologia. Far&ad de Medicina, Universidad Complutense, Madrid, Spain. Supported by NIH grants HL1745 1 and HL27038. Dr. Tamargo was supported by CAICYT grant 2074/83. Reprint requests: Dr. Mario Vassalle, Department of Physiology Box 31, SUNY, Health Science Center, 450 Clarkson Avenue, Brooklyn, NY 11203. and vice versa.1,2 The mechanisms underlying this calcium-related change in the slope of diastolic de- polarization have not been clarified. Since high [Cal, causes an oscillatory potential (V,,),‘-’ the steepening could be due to the super- imposition of V,, on DD. It seems less likely that V,, would steepen DD at normal or low [Cal,, but this possibility cannot be ruled out u priori since the rate of discharge must be taken into consideration. Thus, even in normal [Cal,, repetitive voltage clamp steps can induce the transient inward oscillatory current (I,,) that underlies V,,,4 and an increased rate of dis- 349