Effects of endogenous calcium transport inhibitor from heart muscle on the active calcium uptake and passive calcium release properties of sarcoplasmic reticulum

Abstract

In the present study, the effects of the cytosolic Ca2+ transport inhibitor on ATP-dependent Ca2+ uptake by, and unidirectional passive Ca2+ release from, sarcoplasmic reticulum enriched membrane vesicles were examined in parallel experiments to determine whether inhibitor-mediated enhancement in Ca2+ efflux contributes to inhibition of net Ca2+ uptake. When assays were performed at pH 6.8 in the presence of oxalate, low concentrations (less than 100 micrograms/mL) of the inhibitor caused substantial inhibition of Ca2+ uptake by SR (28-50%). At this pH, low concentrations of the inhibitor did not cause enhancement of passive Ca2+ release from actively Ca2+-loaded sarcoplasmic reticulum. Under these conditions, high concentrations (greater than 100 micrograms/mL) of the inhibitor caused stimulation of passive Ca2+ release but to a much lesser extent when compared with the extent of inhibition of active Ca2+ uptake (i.e., twofold greater inhibition of Ca2+ uptake than stimulation of Ca2+ release). When Ca2+ uptake and release assays were carried out at pH 7.4, the Ca2+ release promoting action of the inhibitor became more pronounced, such that the magnitude of enhancement in Ca2+ release at varying concentrations of the inhibitor (20-200 micrograms/mL) was not markedly different from the magnitude of inhibition of Ca2+ uptake. In the absence of oxalate in the assay medium, inhibition of Ca2+ uptake was observed at alkaline but not acidic pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Appearance of Cytosolic Albumin-Like Protein in Microsomal Fraction of Isolated Rabbit Heart during Global Ischemia.

“…In spite of the findings by Narayanan et al [1,3,7,21, 23] and Chiesi et al [2,4], the physiological role of the antagonist protein still remains to be established. However, Chiesi et al pointed out that the antagonist protein is located at the A/I junction in muscle, where transverse tubules reside in mammalian striated muscular cells [24].…”

“…[2,4] later corroborated the occurrence of such proteins in the cardiac cytosol of guinea pigs. Narayanan et al [3] reported that the inhibitory protein did not disturb the Ca2+ release process from the SR in the presence of oxalate, whereas Chiesi and Schwaller [2] showed accelerated Ca2+ release from passively Ca2+-loaded SR. Narayanan et al [21] later reported two aspects of the inhibitor, activation of Ca2+ uptake at pH 6.8 and inhibition at pH 7.4. Chiesi et al [2,4] identified the inhibitor protein as an isoform of actin, a major component of contractile proteins, and the antagonist protein as f3-actinin, now called muscle albumin.…”