Cumulative depletions of extracellular calcium in rabbit ventricular muscle monitored with calcium-selective microelectrodes

Donald M Bers, K. T. MacLeod

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Transient changes of extracellular free calcium in rabbit ventricular muscle under nonsteady state conditions were measured with double-barreled calcium microelectrodes. Resumption of stimulation after a rest interval produces a cumulative decrease of extracellular free calcium often by more than 10% (with bulk extracellular free calcium = 0.2 mM). The extracellular free calcium returns to the bulk value as a new steady state is achieved. The changes of extracellular free calcium recorded presumably represent net calcium uptake and loss by cardiac muscle cells. These cumulative extracellular free calcium depletions are blocked by 0.5 mM cobalt and 1 μM nifedipine and are increased to 167 ± 11% of control by the calcium agonist Bay k 8644 (1 μM) and to 620 ± 150% of control by increasing stimulus frequency from 0.2-2 Hz. Caffeine (10 mM) inhibits the cumulative extracellular free calcium depletions, probably by rendering the sarcoplasmic reticulum unable to accumulate calcium. It is proposed that the extracellular free calcium depletions recorded represent, in large part, calcium which has entered the cells and has been taken up by the sarcoplasmic reticulum (which had become depleted of calcium during the rest interval). Nifedipine and cobalt inhibit these cumulative depletions presumably by preventing the calcium entry which could subsequently be accumulated by the sarcoplasmic reticulum. The net cellular calcium uptake produced by such a post-rest stimulation protocol can also be inhibited by 1-3 μM acetylstrophanthidin and reduction of extracellular sodium to 70 mM. Acetylstrophanthidin and low extracellular sodium would be expected to shift the sodium-calcium exchange in favor of increased calcium uptake, which may, in turn, prevent the loss of sarcoplasmic reticulum calcium during the rest interval. This would limit the amount of calcium which the sarcoplasmic reticulum could take up with subsequent activation. In contrast to the results with caffeine, ryanodine (1 μM) increases the magnitude and rate of calcium uptake after a rest interval, indicative of a fundamental difference in the actions of caffeine and ryanodine. When stimulation is stopped in the presence of ryanodine, extracellular free calcium increases much faster than the control. This suggests that ryanodine may enhance calcium uptake by the sarcoplasmic reticulum during repetitive stimulation and may enhance calcium efflux from the sarcoplasmic reticulum during quiescence. These experiments provide insight into transsarcolemmal calcium movements and certain aspects of cellular calcium regulation.

Original languageEnglish (US)
Pages (from-to)769-782
Number of pages14
JournalCirculation Research
Volume58
Issue number6
StatePublished - 1986

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Microelectrodes
Rabbits
Calcium
Muscles
Sarcoplasmic Reticulum
Ryanodine
Caffeine
Sodium
Nifedipine
Cobalt

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Cumulative depletions of extracellular calcium in rabbit ventricular muscle monitored with calcium-selective microelectrodes. / Bers, Donald M; MacLeod, K. T.

In: Circulation Research, Vol. 58, No. 6, 1986, p. 769-782.

Research output: Contribution to journalArticle

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abstract = "Transient changes of extracellular free calcium in rabbit ventricular muscle under nonsteady state conditions were measured with double-barreled calcium microelectrodes. Resumption of stimulation after a rest interval produces a cumulative decrease of extracellular free calcium often by more than 10{\%} (with bulk extracellular free calcium = 0.2 mM). The extracellular free calcium returns to the bulk value as a new steady state is achieved. The changes of extracellular free calcium recorded presumably represent net calcium uptake and loss by cardiac muscle cells. These cumulative extracellular free calcium depletions are blocked by 0.5 mM cobalt and 1 μM nifedipine and are increased to 167 ± 11{\%} of control by the calcium agonist Bay k 8644 (1 μM) and to 620 ± 150{\%} of control by increasing stimulus frequency from 0.2-2 Hz. Caffeine (10 mM) inhibits the cumulative extracellular free calcium depletions, probably by rendering the sarcoplasmic reticulum unable to accumulate calcium. It is proposed that the extracellular free calcium depletions recorded represent, in large part, calcium which has entered the cells and has been taken up by the sarcoplasmic reticulum (which had become depleted of calcium during the rest interval). Nifedipine and cobalt inhibit these cumulative depletions presumably by preventing the calcium entry which could subsequently be accumulated by the sarcoplasmic reticulum. The net cellular calcium uptake produced by such a post-rest stimulation protocol can also be inhibited by 1-3 μM acetylstrophanthidin and reduction of extracellular sodium to 70 mM. Acetylstrophanthidin and low extracellular sodium would be expected to shift the sodium-calcium exchange in favor of increased calcium uptake, which may, in turn, prevent the loss of sarcoplasmic reticulum calcium during the rest interval. This would limit the amount of calcium which the sarcoplasmic reticulum could take up with subsequent activation. In contrast to the results with caffeine, ryanodine (1 μM) increases the magnitude and rate of calcium uptake after a rest interval, indicative of a fundamental difference in the actions of caffeine and ryanodine. When stimulation is stopped in the presence of ryanodine, extracellular free calcium increases much faster than the control. This suggests that ryanodine may enhance calcium uptake by the sarcoplasmic reticulum during repetitive stimulation and may enhance calcium efflux from the sarcoplasmic reticulum during quiescence. These experiments provide insight into transsarcolemmal calcium movements and certain aspects of cellular calcium regulation.",
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