Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, C130
Mitochondria adjust intracellular Ca2+ signaling regime to a pattern of neurotransmitter release
N. Fedirko1, O. Kopach1, I. Kruglikov1, N. Voitenko1
1. General Physiology of Nervous System, Bogomoletz Institute of Physiology, Kiev, Ukraine.
The agonist-induced secretion of fluid and electrolytes in acinar cells is governed by Ca2+ signals originated from the endoplasmic reticulum (ER) followed by a store-operated Ca2+ entry (SOCE). During tasting and chewing food the frequency of parasympathetic stimulation increases up to ten-fold, entailing cells to adapt its Ca2+ machinery to promote ER refilling and ensure sustained SOCE by yet unknown mechanism. Male 150-200 g Wistar rats (6-7 weeks old) were used in all experiments. Acinar cells were acutely isolated from the submandibular salivary gland using collagenase treatment, as described previously (Fedirko et al. 2006; Kopach et al. 2008). By employing a combination of fluorescent Ca2+ imaging in the cytoplasm and inside cellular organelles (ER and mitochondria) we found that under the sustained stimulation SOCE is dramatically increased proportionally to the degree of ER depletion. Furthermore, the cell adapts its Ca2+ handling system directing more Ca2+ into mitochondria via microdomains of high [Ca2+] providing positive feedback on SOCE, whereas intra-mitochondrial tunneling provides adequate ER refilling. In the absence of an agonist the bulk of ER refilling occurs through a direct Ca2+-ATPase-mediated uptake from under the plasma membrane. In conclusion, mitochondria play a key role in the maintenance of sustained SOCE and ER refilling, being an intrinsic adaptation mechanism ensuring long-lasting cellular responses.
Where applicable, experiments conform with Society ethical requirements