Changes of SERCA activity have only modest effects on sarcoplasmic reticulum Ca<SUP>2+</SUP> content in rat ventricular myocytes

Bode, EF ORCID: 0000-0003-3754-6026, Briston, SJ, Overend, CL, O'Neill, SC, Trafford, AW and Eisner, DA (2011) Changes of SERCA activity have only modest effects on sarcoplasmic reticulum Ca<SUP>2+</SUP> content in rat ventricular myocytes. JOURNAL OF PHYSIOLOGY-LONDON, 589 (19). pp. 4723-4729.

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Abstract

Changes of the activity of the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) affect the amplitude of the systolic Ca(2+) transient and thence cardiac contractility. This is thought to be due to alterations of SR Ca(2+) content. Recent work on mice in which the expression of SERCA is decreased found that a large reduction of SERCA expression resulted in a proportionately much smaller decrease of SR Ca(2+) content. The aim of the current work was to investigate the quantitative nature of the dependence of both the amplitude of the systolic Ca(2+) transient and SR Ca(2+) content on SERCA activity during acute partial inhibition of SERCA. Experiments were performed on rat ventricular myocytes. Brief application of thapsigargin (1 μm) resulted in a decrease of SERCA activity as measured from the rate of decay of the systolic Ca(2+) transient. This was accompanied by a decrease in the amplitude of the systolic Ca(2+) transient which was linearly related to that of SERCA activity. However, the fractional decrease in the SR Ca(2+) content was much less than that of SERCA activity. On average SR Ca(2+) content was proportional to SERCA activity raised to the 0.38 ± 0.07 power. This shallow dependence of SR content on SERCA activity arises because Ca(2+) release is a steep function of SR Ca(2+) content. In contrast SR Ca(2+) content was increased 4.59 ± 0.40 (n = 8)-fold by decreasing ryanodine receptor opening with tetracaine (1 mm). Therefore a modest decrease of SR Ca(2+) content results in a proportionately larger fall of Ca(2+) release from the SR which can balance a larger initiating decrease of SERCA. In conclusion, the shallow dependence of SR Ca(2+) content on SERCA activity is expected for a system in which small changes of SR Ca(2+) content produce larger effects on the amplitude of the systolic Ca(2+) transient.

Item Type:	Article
Uncontrolled Keywords:	Sarcoplasmic Reticulum, Heart Ventricles, Myocytes, Cardiac, Animals, Rats, Rats, Wistar, Calcium, Tetracaine, Thapsigargin, Ryanodine Receptor Calcium Release Channel, Myocardial Contraction, Systole, Male, Sarcoplasmic Reticulum Calcium-Transporting ATPases
Depositing User:	Symplectic Admin
Date Deposited:	07 Apr 2017 13:06
Last Modified:	12 Oct 2023 01:43
DOI:	10.1113/jphysiol.2011.211052
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3006880