[Na+] in the subsarcolemmal 'fuzzy' space and modulation of [Ca2+]i and contraction in cardiac myocytes

The strength of the heart beat depends on the amplitude and time course of the transient increase in [Ca2+] in the myocytes with each cycle. [Na+](i) modulates cardiac contraction through its effect on the Ca2+ flux through the Na/Ca exchanger. Cardiac excitation-contraction coupling has been postulated to occur in a microdomain or 'fuzzy' space at the junction of the T-tubules and the sarcoplasmic reticulum. This 'fuzzy' space is well described for the Ca2+ fluxes and the interaction between the L-type Ca2+ channel, the Ca2+ release channel of the sarcoplasmic reticulum and the Na/Ca exchanger. Co-localization of the Na+ transporters, in particular the Na/K pump and the Na+ channel, within this 'fuzzy' space is not as well established. The functional and morphological characteristics of the 'fuzzy' space for Na+ and its interaction with the Ca2+ handling suggest that this space is not strictly co-inciding with the Ca2+ microdomain. In this space [Na+] can be several-fold higher or lower than [Na+] in the bulk cytosol. This has implications for modulation of [Ca2+](i) during a single beat as well as during alterations in Na+ fluxes seen in pathological conditions. (C) 2004 Elsevier Ltd. All rights reserved.