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Differentiation induces up-regulation of plasma membrane Ca2+-ATPase and concomitant increase in Ca2+ efflux in human neuroblastoma cell line IMR-32
Journal article   Open access   Peer reviewed

Differentiation induces up-regulation of plasma membrane Ca2+-ATPase and concomitant increase in Ca2+ efflux in human neuroblastoma cell line IMR-32

Yuriy M USACHEV, Sonja L TOUTENHOOFD, Geoffrey M GOELLNER, Emanuel E STREHLER and Stanley A THAYER
Journal of neurochemistry, Vol.76(6), pp.1756-1765
2001
DOI: 10.1046/j.1471-4159.2001.00169.x
PMID: 11259493
url
https://doi.org/10.1046/j.1471-4159.2001.00169.xView
Published (Version of record) Open Access

Abstract

Precise regulation of intracellular Ca(2+) concentration ([Ca(2+)](i)) is achieved by the coordinated function of Ca(2+) channels and Ca(2+) buffers. Neuronal differentiation induces up-regulation of Ca(2+) channels. However, little is known about the effects of differentiation on the expression of the plasma membrane Ca(2+)-ATPase (PMCA), the principal Ca(2+) extrusion mechanism in neurons. In this study, we examined the regulation of PMCA expression during differentiation of the human neuroblastoma cell line IMR-32. [Ca(2+)](i) was monitored in single cells using indo-1 microfluorimetry. When the Ca(2+)-ATPase of the endoplasmic reticulum was blocked by cyclopiazonic acid, [Ca(2+)](i) recovery after small depolarization-induced Ca(2+) loads was governed primarily by PMCAs. [Ca(2+)](i) returned to baseline by a process described by a monoexponential function in undifferentiated cells (tau = 52 +/- 4 s; n = 25). After differentiation for 12-16 days, the [Ca(2+)](i) recovery rate increased by more than threefold (tau = 17 +/- 1 s; n = 31). Western blots showed a pronounced increase in expression of three major PMCA isoforms in IMR-32 cells during differentiation, including PMCA2, PMCA3 and PMCA4. These results demonstrate up-regulation of PMCAs on the functional and protein level during neuronal differentiation in vitro. Parallel amplification of Ca(2+) influx and efflux pathways may enable differentiated neurons to precisely localize Ca(2+) signals in time and space.
Cell Physiology Fundamental and applied biological sciences. Psychology Biological and medical sciences Molecular and cellular biology Cell differentiation, maturation, development, hematopoiesis

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