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Regulation of systolic [Ca 2+ ] i and cellular Ca 2+ flux balance in rat ventricular myocytes by SR Ca 2+ , L‐type Ca 2+ current and diastolic [Ca 2+ ] i
Author(s) -
Dibb K. M.,
Eisner D. A.,
Trafford A. W.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.141473
Subject(s) - flux (metallurgy) , myocyte , chemistry , physics , biology , endocrinology , organic chemistry
The force–frequency response is an important physiological mechanism regulating cardiac output changes and is accompanied in vivo by β‐adrenergic stimulation. We sought to determine the role of sarcoplasmic reticulum (SR) Ca 2+ content and L‐type current ( I Ca‐L ) in the frequency response of the systolic Ca 2+ transient alone and during β‐adrenergic stimulation. Experiments (on single rat ventricular myocytes) were designed to be as physiological as possible. Under current clamp stimulation SR Ca 2+ content increased in line with stimulation frequency (1–8 Hz) but the systolic Ca 2+ transient was maximal at 6 Hz. Under voltage clamp, increasing frequency decreased both systolic Ca 2+ transient and I Ca‐L . Normalizing peak I Ca‐L by altering the test potential decreased the Ca 2+ transient amplitude less than an equivalent reduction achieved through changes in frequency. This suggests that, in addition to SR Ca 2+ content and I Ca‐L , another factor, possibly refractoriness of Ca 2+ release from the SR contributes. Under current clamp, β‐adrenergic stimulation (isoprenaline, 30 n m ) increased both the Ca 2+ transient and the SR Ca 2+ content and removed the dependence of both on frequency. In voltage clamp experiments, β‐adrenergic stimulation still increased SR Ca 2+ content yet there was an inverse relation between frequency and Ca 2+ transient amplitude and I Ca‐L . Diastolic [Ca 2+ ] i increased with stimulation frequency and this contributed substantially (69.3 ± 6% at 8 Hz) to the total Ca 2+ efflux from the cell. We conclude that Ca 2+ flux balance is maintained by the combination of increased efflux due to elevated diastolic [Ca 2+ ] i and a decrease of influx on I Ca‐L on each pulse.