Systolic [Ca2+ ]i regulates diastolic levels in rat ventricular myocytes

Sankaranarayanan, R, Kistamas, K, Greensmith, DJ ORCID:, Venetucci, LA and Eisner, DA 2017, 'Systolic [Ca2+ ]i regulates diastolic levels in rat ventricular myocytes' , The Journal of Physiology, 595 (16) , pp. 5545-5555.

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[Ca2+]i must be low enough in diastole so that the ventricle is relaxed and can refill with blood. Interference with this will impair relaxation. The factors responsible for regulation of diastolic [Ca2+]i, in particular the relative roles of the sarcoplasmic reticulum (SR) and surface membrane are unclear. We investigated the effects on diastolic [Ca2+]i that result from the changes of Ca cycling known to occur in heart failure. Experiments were performed using Fluo-3 in voltage-clamped rat ventricular myocytes. Increasing stimulation frequency increased diastolic [Ca2+]i. This increase of [Ca2+]i was larger when SR function was impaired either by making the RyR leaky (with caffeine or ryanodine) or by decreasing SERCA activity with thapsigargin. The increase of diastolic [Ca2+]i produced by interfering with the SR was accompanied by a decrease of the amplitude of the systolic Ca transient such that there was no change of time-averaged [Ca2+]i. Time-averaged [Ca2+]i was increased by β-adrenergic stimulation with isoprenaline and increased in a saturating manner with increased stimulation frequency; average [Ca2+]i was a linear function of Ca entry per unit time. Diastolic and time-averaged [Ca2+]i were decreased by decreasing the L-type Ca current (with 50 μm cadmium chloride). We conclude that diastolic [Ca2+]i is controlled by the balance between Ca entry and efflux during systole. Furthermore, manoeuvres which decrease the amplitude of the Ca transient (without decreasing Ca influx) will therefore increase diastolic [Ca2+]i. This identifies a novel mechanism whereby changes of the amplitude of the systolic Ca transient control diastolic [Ca2+]i.

Item Type: Article
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: The Journal of Physiology
Publisher: Wiley
ISSN: 1469-7793
Related URLs:
Funders: British Heart Foundation
Depositing User: D Greensmith
Date Deposited: 23 Jun 2017 14:22
Last Modified: 15 Feb 2022 22:09

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