Correlation of the localization of La+++ with its effects on Ca++ exchange in cultured rat heart cells is examined with the use of a recently developed technique. 75% of cellular Ca++ is exchangeable and is completely accounted for by two kinetically defined phases. The rapidly exchangeable phase has a t ½ = 1.15 min and accounts for 1 1 mmoles Ca++/kg wet cells or 43% of the exchangeable Ca++ (cells perfused with [Ca++]o = 1 mM) Phase 2 has a t ½ = 19.2 min and accounts for 1.5 mmoles Ca++/kg wet cells or 57% of the exchangeable Ca++. 0.5 mM [La+++]o displaces 0 52 mmoles Ca++/kg wet cells—all from phase 1—and almost completely abolishes subsequent Ca++ influx and efflux The presence of La+++ in the washout converts the washout pattern to a single phase system with a t ½ = 124 min. The effects upon Ca++ exchange are coincident with abolition of contractile tension but regenerative depolarization of the tissue is maintained Electron microscope localization of the La+++ places it exclusively in the external lamina or basement membrane of the cells. The study indicates that negatively charged sites in the basement membrane play a crucial role in the E-C coupling process in heart muscle

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