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. 1996 Jan;117(1):5–12. doi: 10.1111/j.1476-5381.1996.tb15147.x

Propofol regulation of calcium entry pathways in cultured A10 and rat aortic smooth muscle cells.

Y T Xuan 1, P S Glass 1
PMCID: PMC1909380  PMID: 8825336

Abstract

1. We have investigated the effect of propofol, an intravenous anaesthetic, on the intracellular calcium concentration ([Ca2+]i), Ca2+ entry pathways and on inositol phosphate formation in vascular smooth muscle cells. [Ca2+]i and Ca2+ flux were monitored with the Ca(2+)-sensitive fluorescent dye, fura-2, and by 45Ca2+ uptake. Production of labelled inositol phosphates was analysed by anion-exchange chromatography. 2. Treatment of the cells with endothelin-1 (ET-1) increased formation of inositol phosphates and elevated [Ca2+]i due to both release of Ca2+ from intracellular pools and prolonged entry of Ca2+ from outside the cell. Propofol reduced production of inositol phosphates mediated by ET-1 and arginine vasopressin which activate phospholipase C. 3. The sustained Ca2+ entry stimulated by ET-1 was found to occur through the activation of L-type Ca channels. This was inhibited by propofol in a dose-dependent manner. 4. Activation of protein kinase C (PKC) by phorbol esters activated a pharmacologically-similar channel and produced a similar change in [Ca2+]i due to Ca2+ entry. The entry was blocked by an L-type channel antagonist, nicardipine and by the anaesthetic drug, propofol. 5. Treatment of the cells with thapsigargin, a selective inhibitor of the sarcoplasmic reticulum Ca(2+)-ATPase, also elevated [Ca2+]i by inducing the release of intracellular Ca2+ and the continued entry of extracellular Ca2+ through a nicardipine-insensitive Ca channel. Neither release nor entry induced by thapsigargin was affected by propofol. 6. These findings suggest that propofol selectively inhibits Ca2+ entry through the L-type channel induced by ET-1 and phorbol esters but has no effects on Ca2+ entry via the nicardipine-insensitive channel and on Ca2+ release from intracellular pools initiated by thapsigargin. This may represent one of the mechanisms responsible for propofol-induced vasodilatation.

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Selected References

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