Lanthanum in heart cell culture. Effect on calcium exchange correlated with its localization

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 (1/2) = 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 (1/2) = 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 (1/2) = 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