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Adv Exp Med Biol. 2013;961:375-83. doi: 10.1007/978-1-4614-4756-6_32.

T-tubule remodelling and ryanodine receptor organization modulate sodium-calcium exchange.

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Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.


The Na(+)/Ca(2+) exchanger (NCX) is a key regulator of intracellular Ca(2+) in cardiac myocytes, predominantly contributing to Ca(2+) 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 Ca(2+) channels face ryanodine receptors (RyRs), the Ca(2+) 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 Ca(2+) 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 Ca(2+) events. The loss of T-tubules and the effects on RyR function and NCX modulation are explored, as well as quantitative measurement of local Ca(2+) gradients at the level of the dyadic space.

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