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

Sankaranarayanan, R; Kistamas, K; Greensmith, DJ; Venetucci, LA; Eisner, DA

Abstract

[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.

Citation

Sankaranarayanan, R., Kistamas, K., Greensmith, D., Venetucci, L., & Eisner, D. (2017). Systolic [Ca2+ ]i regulates diastolic levels in rat ventricular myocytes. Journal of Physiology, 595(16), 5545-5555. https://doi.org/10.1113/JP274366

• Journal Article Type: Article
• Acceptance Date: Jun 13, 2017
• Online Publication Date: Jun 15, 2017
• Publication Date: Jun 15, 2017
• Deposit Date: Jun 23, 2017
• Publicly Available Date: Aug 23, 2017
• Journal: The Journal of Physiology
• Print ISSN: 0022-3751
• Publisher: Wiley
• Volume: 595
• Issue: 16
• Pages: 5545-5555
• DOI: https://doi.org/10.1113/JP274366
• Publisher URL: http://dx.doi.org/10.1113/JP274366
• Related Public URLs: http://physoc.onlinelibrary.wiley.com/hub/journal/10.1111/(ISSN)1469-7793/