Cardiovascular
Presence of store-operated Ca2+ entry in C57BL/6J mouse ventricular myocytes and its suppression by sevoflurane

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Background

Store-operated Ca2+ entry (SOCE) has been implicated in various pathological conditions of the heart including ischaemia/reperfusion and ventricular hypertrophy. This study investigated the effects of sevoflurane on SOCE.

Methods

Fluorescence imaging was performed on fluo-3- and mag-fluo-4-loaded mouse ventricular myocytes to measure the cytosolic and intraluminal sarcoplasmic reticulum (SR) Ca2+ levels, respectively, using a confocal laser scanning microscope. Whole-cell membrane currents were recorded using the patch-clamp technique. Ventricular myocytes were exposed to thapsigargin and angiotensin II to deplete SR Ca2+ stores and thereby activate SOCE.

Results

The combined application of thapsigargin and angiotensin II to the Ca2+-free medium evoked a significant decrease in the SR Ca2+ levels, which was followed by the elevation of cytosolic Ca2+ and the development of cellular hypercontracture upon subsequent addition of extracellular Ca2+. This cytosolic Ca2+ elevation was inhibited by 2-aminoethoxydiphenyl borate but not by verapamil and KB-R7943, which indicates that SOCE was present in mouse ventricular myocytes. Sevoflurane concentration-dependently inhibited the SOCE-mediated Ca2+ overload (IC50 of 137 μM, which corresponds to 0.96%) with a significant reduction occurring at concentrations of ≥2%. Patch-clamp experiments revealed that the SOCE current was also concentration-dependently blocked by sevoflurane (IC50 of 144 μM, which corresponds to 1.0%).

Conclusions

Sevoflurane at concentrations of ≥2% significantly inhibits the SOCE activity and prevents the resultant cellular Ca2+ overload that leads to hypercontracture in ventricular myocytes. This inhibitory action may be involved in the cardioprotective effect of sevoflurane against Ca2+ overload-mediated injury.

Key words

anaesthetics volatile, sevoflurane
heart, myocytes
ions, ion channels
mouse
physiology, electrophysiology (ion channels)

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