Stimulation-dependent facilitation of the high threshold calcium current in guinea-pig ventricular myocytes.
1. Stimulation-dependent modulation of Ca currents was examined in guinea-pig ventricular myocytes at room temperature. Whole-cell recordings of Ca currents were made under conditions which minimized ionic fluxes through other channels. 2. Stimulation from rest at a rate of 2 Hz resulted in a decrease of the low threshold Ca current within one pulse and facilitation of the high threshold Ca current within five pulses. Facilitation was associated with a reduction in the rate of inactivation. 3. Pulse durations as short as 10 ms facilitated the high threshold Ca current in subsequent pulses. Facilitation produced by a single pulse decayed with a half-time of several seconds. 4. Substitution of Ba2+ or Sr2+ for external Ca2+ reduced the rate of inactivation of the high threshold Ca current and abolished facilitation of the current. 5. Facilitation persisted with 40 microM-Ruthenium Red added to the internal solution or 0.2-2 microM-ryanodine added to the bath solution to reduce Ca2+ release from the sarcoplasmic reticulum. 6. Facilitation was modulated by isoprenaline. Low concentrations of isoprenaline (5-10 nM) increased the amount of facilitation. Isoprenaline (1 microM) increased the Ca current approximately 3-fold, however, facilitation was nearly abolished. 7. Caffeine (0.5 and 1 mM) affected the Ca current and facilitation in a manner similar to 1 microM-isoprenaline. It increased the Ca currents approximately 2.5-fold and facilitation was not observed. 8. We conclude that stimulation-dependent facilitation of the high threshold Ca current is mediated by calcium and hypothesize that calcium affects a site near the Ca channel that modifies the rate of inactivation. The common actions of caffeine and high concentrations of isoprenaline suggest that calcium modulates a phosphorylation step.
Zygmunt
A C
AC
Department of Physiology, Oregon Health Sciences University, Portland 97201.
Maylie
J
J
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002469:Cell Separation; D004594:Electrophysiology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D016276:Ventricular Function
D015220:Calcium Channels; D012433:Ryanodine; D002110:Caffeine; D007545:Isoproterenol