title: [Na(+)] in the subsarcolemmal 'fuzzy' space and modulation of [Ca(2+)](i) and contraction in cardiac myocytes.
abstract: The strength of the heart beat depends on the amplitude and time course of the transient increase in [Ca(2+)] in the myocytes with each cycle. [Na(+)](i) modulates cardiac contraction through its effect on the Ca(2+) 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 Ca(2+) fluxes and the interaction between the L-type Ca(2+) channel, the Ca(2+) 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 Ca(2+) handling suggest that this space is not strictly co-inciding with the Ca(2+) microdomain. In this space [Na(+)] can be several-fold higher or lower than [Na(+)] in the bulk cytosol. This has implications for modulation of [Ca(2+)](i) during a single beat as well as during alterations in Na(+) fluxes seen in pathological conditions.
authors.affiliation: Interdisciplinary Research Center, Katholieke University of Leuven, Campus Kortrijk, Kortrijk, Belgium. Karin.Sipido@med.kuleuven.ac.be
authors.forename: Fons
authors.initials: F
authors.lastname: Verdonck
authors.forename: Kanigula
authors.initials: K
authors.lastname: Mubagwa
authors.forename: Karin R
authors.initials: KR
authors.lastname: Sipido
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012508:Sarcolemma / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium