T channels and steroid biosynthesis: in search of a link with mitochondria

Abstract

The activity of T-type Ca2+ channels has been associated for a long time with steroid biosynthesis in adrenal cortical cells. Because Ca2+-dependent, rate-limiting steps of steroidogenesis have been shown to occur within the mitochondria, a functional link between these organelles and T-type channels has been thoroughly investigated. Based on several experimental data, a model has been proposed in which plasma-membrane-embedded T channels specifically bring calcium entering the cell in proximity of a pumping site of the endoplasmic reticulum. The quasi direct transfer of Ca2+ from the extracellular medium into the lumen of the e.r. would be a specific feature insured by T channels, not by other voltage-operated calcium channels. The e.r. would then act as a sort of Ca2+ pipeline, carrying the cation to the proximity of mitochondria, where it would be released, upon activation of the inositol 1,4,5-trisphosphate receptor, before being immediately and avidly taken up by the organelle. A strict structural organization must be maintained at each extremity of the pipeline in order to optimize the specificity and the efficacy of this signal transduction. Both functional and structural evidences supporting this model of calcium transport within steroidogenic glomerulosa cells are reviewed in the present article.