Stimulation-dependent facilitation of the high threshold calcium current in guinea-pig ventricular myocytes

A. C. Zygmunt, James Maylie

Research output: Contribution to journalArticle

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Abstract

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 μM-Ruthenium Red added to the internal solution or 0.2-2 μM-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 μM) 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 μM-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.

Original languageEnglish (US)
Pages (from-to)653-671
Number of pages19
JournalJournal of Physiology
Volume428
StatePublished - 1990

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Isoproterenol
Muscle Cells
Guinea Pigs
Calcium
Caffeine
Ruthenium Red
Ryanodine
Sarcoplasmic Reticulum
Patch-Clamp Techniques
Baths
Phosphorylation
Temperature

ASJC Scopus subject areas

  • Physiology

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Stimulation-dependent facilitation of the high threshold calcium current in guinea-pig ventricular myocytes. / Zygmunt, A. C.; Maylie, James.

In: Journal of Physiology, Vol. 428, 1990, p. 653-671.

Research output: Contribution to journalArticle

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N2 - 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 μM-Ruthenium Red added to the internal solution or 0.2-2 μM-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 μM) 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 μM-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.

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