Astrocytes refill intracellular Ca2+ stores in the absence of cytoplasmic [Ca2+] elevation: a functional rather than a structural ability |
| |
Authors: | Grimaldi Maurizio |
| |
Institution: | Laboratory of Neuropharmacology, Department of Biochemistry, Drug Discovery Division, Southern Research Institute, Birmingham, AL 35025, USA. grimaldi@sri.org |
| |
Abstract: | Capacitative Ca(2+) entry (CCE) is a phenomenon triggered by depletion of Ca(2+) content in intracellular stores (ICS). Data about this phenomenon in astrocytes are limited. We analyzed CCE in astrocytes by means of fura-2 based digital imaging. We found that in astrocytes CCE is not associated with an increase of cytosolic Ca(2+) concentration (Ca(2+)](i)), although ICS are efficiently refilled. We used Mn(2+), thapsigargin and prolonged ATP exposure to show that CCE is not associated with cytosolic diffusion of Ca(2+) entering astrocytes. Our data suggest that the ion is being quickly sequestered in the ICS by the smooth endoplasmic reticulum Ca(2+)-ATP-ase (SERCA). Several experiments were carried out with the goal of failing the efficient uptake in the endoplasmic reticulum (ER). In fact, inhibition of SERCA activity, increased extracellular Ca(2+)](i) or pharmacologic potentiation of CCE all caused Ca(2+)](i) elevation during CCE, suggesting that the control of this phenomenon could have physiologic and pathological relevance. The molecular components involved in CCE have been proposed to be organized in a multi-molecular complex tethered by cytoskeleton components and arranged via a secretion coupling model. We show here that the efficient routing of Ca(2+) into the ICS in astrocytes is not affected by disruption of cytoskeleton organization or Golgi's function, but it is instead linked to the high efficiency of SERCA. We conclude that depleted ICS in astrocytes are efficiently refilled by CCE activation, although Ca(2+) influx is not accompanied by elevation of Ca(2+)](i). This ability seems to be functional rather than structural in nature. |
| |
Keywords: | astrocyte capacitative Ca2+ entry smooth endoplasmic reticulum Ca2+ ATPase store depletion‐operated Ca2+ channels endoplasmic reticulum |
本文献已被 PubMed 等数据库收录! |
|