Abstract
The Na+/Ca2+ exchanger (NCX) is a key regulator of intracellular Ca2+ in cardiac myocytes, predominantly contributing to Ca2+ removal during the diastolic relaxation process but also modulating excitation-contraction coupling. NCX is preferentially located in the T-tubules and can be close to or within the dyad, where L-type Ca2+ channels face ryanodine receptors (RyRs), the Ca2+ release channels of the sarcoplasmic reticulum. However, especially in larger animals, not all RyRs are in dyads or adjacent to T-tubules, and a substantial fraction of Ca2+ release from the sarcoplasmic reticulum thus occurs at distance from NCX. This chapter deals with the functional consequences of NCX location and how NCX can modulate diastolic and systolic Ca2+ events. The loss of T-tubules and the effects on RyR function and NCX modulation are explored, as well as quantitative measurement of local Ca2+ gradients at the level of the dyadic space.
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Acknowledgements
The authors acknowledge support from EC FP7/2007–2013 under grant agreement no. HEALTH-F2-2009-241526, EUTrigTreat (to K.R.S.).
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Sipido, K.R., Acsai, K., Antoons, G., Bito, V., Macquaide, N. (2013). T-Tubule Remodelling and Ryanodine Receptor Organization Modulate Sodium-Calcium Exchange. In: Annunziato, L. (eds) Sodium Calcium Exchange: A Growing Spectrum of Pathophysiological Implications. Advances in Experimental Medicine and Biology, vol 961. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4756-6_32
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DOI: https://doi.org/10.1007/978-1-4614-4756-6_32
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