Picture child's feet next to pens, pencils and paper

Open Access research that is helping to improve educational outcomes for children

Strathprints makes available scholarly Open Access content by researchers in the School of Education, including those researching educational and social practices in curricular subjects. Research in this area seeks to understand the complex influences that increase curricula capacity and engagement by studying how curriculum practices relate to cultural, intellectual and social practices in and out of schools and nurseries.

Research at the School of Education also spans a number of other areas, including inclusive pedagogy, philosophy of education, health and wellbeing within health-related aspects of education (e.g. physical education and sport pedagogy, autism and technology, counselling education, and pedagogies for mental and emotional health), languages education, and other areas.

Explore Open Access education research. Or explore all of Strathclyde's Open Access research...

Inhibition of mitochondrial calcium uptake rather than efflux impedes calcium release by inositol-1,4,5-trisphosphate-sensitive receptors

Chalmers, S. and McCarron, J.G. (2009) Inhibition of mitochondrial calcium uptake rather than efflux impedes calcium release by inositol-1,4,5-trisphosphate-sensitive receptors. Cell Calcium, 46 (2). pp. 107-113. ISSN 0143-4160

Full text not available in this repository. Request a copy from the Strathclyde author

Abstract

Mitochondria modulate cellular Ca2+ signals by accumulating the ion via a uniporter and releasing it via Na+- or H+-exchange. In smooth muscle, inhibition of mitochondrial Ca2+ uptake inhibits Ca2+ release from the sarcoplasmic reticulum (SR) via inositol-1,4,5-trisphosphate-sensitive receptors (IP3R). At least two mechanisms may explain this effect. First, localised uptake of Ca2+ by mitochondria may prevent negative feedback by cytosolic Ca2+ on IP3R activity, or secondly localised provision of Ca2+ by mitochondrial efflux may maintain IP3R function or SR Ca2+ content. To distinguish between these possibilities the role of mitochondrial Ca2+ efflux on IP3R function was examined. IP3 was liberated in freshly isolated single colonic smooth muscle cells and mitochondrial Na+-Ca2+ exchanger inhibited with CGP-37157 (10 μM). Mitochondria accumulated Ca2+ during IP3-evoked [Ca2+]c rises and released the ion back to the cytosol (within 15 s) when mitochondrial Ca2+ efflux was active. When mitochondrial Ca2+ efflux was inhibited by CGP-37157, an extensive and sustained loading of mitochondria with Ca2+ occurred after IP3-evoked Ca2+ release. IP3-evoked [Ca2+]c rises were initially unaffected, then only slowly inhibited by CGP-37157. IP3R activity was required for inhibition to occur; incubation with CGP-37157 for the same duration without IP3 release did not inhibit IP3R. CGP-37157 directly inhibited voltage-gated Ca2+ channel activity, however SR Ca2+ content was unaltered by the drug. Thus, the gradual decline of IP3R function that followed mitochondrial Na+-Ca2+ exchanger inhibition resulted from a gradual overload of mitochondria with Ca2+, leading to a reduced capacity for Ca2+ uptake. Localised uptake of Ca2+ by mitochondria, rather than mitochondrial Ca2+ efflux, appears critical for maintaining IP3R activity.