Selective Deposition of Lanthanum in Mammalian Cardiac Cell Membranes

Abstract

Perfusion of beating false tendons of the dog heart with ionic lanthanum produced drastic but reversible modifications of the excitability and the transmembrane action potential of Purkinje cells . Ultrastructural examination of these cells revealed the appearance of a fine extracellular precipitate detectable on unstained sections . In addition, specimens perfused with La+++ showed a striking increase in the contrast of the sarcolemma, particularly in gap junctions and in pinocytic vesicles . La+++ deposits were restricted to the cytoplasmic leaflets of the sarcolemma ; no precipitates were found at the plasma membrane of fibroblasts, endothelial and smooth muscle cells, or unmyelinated nerve fibers present in the same specimens . A selective deposition of La+++ was also observed in the sarcolemma of atrial and ventricular cells of dog, rabbit, and cat hearts, as well as in the membrane of the transverse tubular system of ventricular cells . Both the electrophysiological effects and the ultrastructural membrane deposits produced by La+++ disappeared when the specimens were subsequently perfused with phosphate-containing tyrode solution . These results tend to demonstrate that a distinctive feature of the sarcolemma of mammalian cardiac cells is the presence of regions with a high surface density of binding sites for polyvalent cations.

The myocardial cell surface, its histochemistry, and the effect of sialic acid and calcium removal on its stucture and cellular ionic exchange.

“…La 3+ was chosen as one of the histochemical stains because, aside from being a well known cell surface marker, 21 it has well studied effects on muscle function 4 -5 - 22 In addition, La 3+ was used as an ultrastructural marker for changes in membrane permeability in the sialic acid and "zero" Ca 2+ studies. LaCl 3 (American Chemicals), in concentrations between 1 and 5 mM, was added to the standard perfusate buffered with 3 mM HEPES (pH 7.1).…”

Lanthanum Probe Studies of Cellular Pathophysiology Induced by Hypoxia in Isolated Cardiac Muscle

“…The muscle shows evidence of damage in the form of edema, glycogen depletion, and absence of normal dense mitochondrial granules. Intracellular La is evident along the I bands of myofibrils (arrows) and in mitochondria (arrowheads (14)(15)(16)(17)(18)(19). The distinctive accumulation of lanthanum in the mitochondria suggests that the lanthanum probe technique may have detected an abnormality in inner mitochondrial membrane function leading to increased cation transport and accumulation of cations in mitochondria (5,6,(40)(41)(42)(43).…”

“…The major physiological effect of lanthanum, a trivalent ion with electrochemical properties similar to calcium (14), is excitation-contraction uncoupling associated with displacement of calcium from superficial binding sites (15)(16)(17)(18)(19). Several ultrastructural studies have shown that lanthanum selectively binds to the basal lamina-plasma membrane complex and is not visualized ultrastructurally within normal cardiac muscle cells (17)(18)(19)(20)(21). These previous studies indicate that abnormal ultrastructural localization of lanthanum intracellularly can serve as a cytochemical marker of pathophysiological alterations in injured myocardium.…”

“…To study this relationship, an ionic lanthanum probe technique was employed as a cytochemical marker of the progression of cellular injury induced by graded intervals of hypoxia with or without reoxygenation in isolated papillary muscles (8)(9)(10)(11)(12)(13) have characterized the response of normal myocardium to lanthanum (14)(15)(16)(17)(18)(19)(20)(21). The major physiological effect of lanthanum, a trivalent ion with electrochemical properties similar to calcium (14), is excitation-contraction uncoupling associated with displacement of calcium from superficial binding sites (15)(16)(17)(18)(19). Several ultrastructural studies have shown that lanthanum selectively binds to the basal lamina-plasma membrane complex and is not visualized ultrastructurally within normal cardiac muscle cells (17)(18)(19)(20)(21).…”

“…within 10 min; the pH remained in the range of 7.3 to 7.4 throughout the experiments, Of the 64 muscles, 18 controls were maintained in oxygenated medium for 1-3 h after initial stabilization; 19 muscles were subjected to hypoxia for 30 min-3 h after initial stabilization, and 27 muscles were subjected to hypoxia for variable intervals and then reoxygenated. 8 control, 11 hypoxic, and 23 reoxygenated muscles were exposed to lanthanum (La) by replacing the standard Hepes solution with a similar solution containing 5 mM LaCl3 for the last 30 min-1 h in the bath (19). Reoxygenation studies involved reoxygenation with 100% 02 for 30 min followed by an additional hour in oxygenated medium containing La.…”