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  • Propofol induces the elevation of intracellular calcium via morphological changes in intracellular organelles, including the endoplasmic reticulum and mitochondria.

Propofol induces the elevation of intracellular calcium via morphological changes in intracellular organelles, including the endoplasmic reticulum and mitochondria.

European journal of pharmacology (2020-07-19)
Tomoaki Urabe, Yuhki Yanase, Serika Motoike, Kana Harada, Izumi Hide, Shigeru Tanaka, Yasuo M Tsutsumi, Masashi Kawamoto, Norio Sakai
ABSTRACT

Propofol, most frequently used as a general anesthetic due to its versatility and short-acting characteristics, is thought to exert its anesthetic actions via GABAA receptors; however, the precise mechanisms of its adverse action including angialgia remain unclear. We examined the propofol-induced elevation of intracellular calcium and morphological changes in intracellular organelles using SHSY-5Y neuroblastoma cells, COS-7 cells, HEK293 cells, and HUVECs loaded with fluorescent dyes for live imaging. Although propofol (>50 μM) increased intracellular calcium in a dose-dependent manner in these cells, it was not influenced by the elimination of extracellular calcium. The calcium elevation was abolished when intracellular or intraendoplasmic reticulum (ER) calcium was depleted by BAPTA-AM or thapsigargin, respectively, suggesting that calcium was mobilized from the ER. Studies using U-73122, xestospongin C, and dantrolene revealed that propofol-induced calcium elevation was not mediated by G-protein coupled receptors, IP3 receptors, or ryanodine receptors. We performed live imaging of the ER, mitochondria and Golgi apparatus during propofol stimulation using fluorescent dyes. Concomitant with the calcium elevation, the structure of the ER and mitochondria was fragmented and aggregated, and these changes were not reversed during the observation period, suggesting that propofol-induced calcium elevation occurs due to calcium leakage from these organelles. Although the concentration of propofol used in this experiment was greater than that used clinically (30 μM), it is possible that the concentration exceeds 30 μM at the site where propofol is injected, leading the idea that these phenomena might relate to the various propofol-induced adverse effects including angialgia.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2,4-Diisopropylphenol, 98%
Sigma-Aldrich
Thapsigargin, ≥98% (HPLC), solid film
Sigma-Aldrich
Xestospongin C, film