The FASEB Journal, Vol 11, 881-885, Copyright © 1997 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

[Ca2+] microdomains control agonist-induced Ca2+ release in intact HeLa cells

M Montero, MJ Barrero and J Alvarez
Departamento de Bioquimica y Fisiologia, IBGM, Facultad de Medicina, Universidad de Valladolid and CSIC, Spain.

We have monitored specifically the [Ca2+] in the lumen of the endoplasmic reticulum (ER) of intact HeLa cells using an ER-targeted low-Ca2+-affinity aequorin. The steady-state [Ca2+] in the ER was around 600 microM. Histamine induced a concentration-dependent decrease in lumenal [Ca2+], whose rate increased near one order of magnitude and became "quantal" when cytosolic [Ca2+] ([Ca2+]c) was clamped with the Ca2+ chelator BAPTA. This effect was not due to decreased Ca2+ pumping because simultaneous addition of a SERCA inhibitor produced only additive effects. Given that inhibition by [Ca2+]c of the inositol 1,4,5-trisphosphate-gated channels requires a [Ca2+]c much higher than that observed in the bulk cytosol after histamine addition, we conclude that local [Ca2+]c microdomains at the site of release strongly inhibit agonist-induced Ca2+ mobilization in intact cells. This effect should play a key role in the mechanism controlling cytosolic [Ca2+] oscillations and waves, and therefore in the generation of spatio- temporal Ca2+ patterns.

This article has been cited by other articles:

				L. Vay, E. Hernandez-SanMiguel, J. Santo-Domingo, C. D. Lobaton, A. Moreno, M. Montero, and J. Alvarez Modulation of Ca2+ release and Ca2+ oscillations in HeLa cells and fibroblasts by mitochondrial Ca2+ uniporter stimulation J. Physiol., April 1, 2007; 580(1): 39 - 49. [Abstract] [Full Text] [PDF]

				M. Montero, C. D. Lobaton, S. Gutierrez-Fernandez, A. Moreno, and J. Alvarez Modulation of Histamine-induced Ca2+ Release by Protein Kinase C: EFFECTS ON CYTOSOLIC AND MITOCHONDRIAL [Ca2+] PEAKS J. Biol. Chem., December 12, 2003; 278(50): 49972 - 49979. [Abstract] [Full Text] [PDF]

				C. VILLALOBOS, L. NUNEZ, M. MONTERO, A. G. GARCIA, M. T. ALONSO, P. CHAMERO, J. ALVAREZ, and J. GARCIA-SANCHO Redistribution of Ca2+ among cytosol and organella during stimulation of bovine chromaffin cells FASEB J, March 1, 2002; 16(3): 343 - 353. [Abstract] [Full Text] [PDF]

				M. Montero, M. T. Alonso, A. Albillos, J. García-Sancho, and J. Alvarez Mitochondrial Ca2+-induced Ca2+ Release Mediated by the Ca2+ Uniporter Mol. Biol. Cell, January 1, 2001; 12(1): 63 - 71. [Abstract] [Full Text]

				A. Takahashi, P. Camacho, J. D. Lechleiter, and B. Herman Measurement of Intracellular Calcium Physiol Rev, October 1, 1999; 79(4): 1089 - 1125. [Abstract] [Full Text] [PDF]

				P. Maechler, E. D. Kennedy, E. Sebo, A. Valeva, T. Pozzan, and C. B. Wollheim Secretagogues Modulate the Calcium Concentration in the Endoplasmic Reticulum of Insulin-secreting Cells. STUDIES IN AEQUORIN-EXPRESSING INTACT AND PERMEABILIZED INS-1 CELLS J. Biol. Chem., April 30, 1999; 274(18): 12583 - 12592. [Abstract] [Full Text] [PDF]

				M. T. Alonso, M. J. Barrero, P. Michelena, E. Carnicero, I. Cuchillo, A. G. Garcia, J. Garcia-Sancho, M. Montero, and J. Alvarez Ca2+-induced Ca2+ Release in Chromaffin Cells Seen from inside the ER with Targeted Aequorin J. Cell Biol., January 25, 1999; 144(2): 241 - 254. [Abstract] [Full Text] [PDF]

				J. Meldolesi and T. Pozzan The Heterogeneity of ER Ca2+ Stores Has a Key Role in Nonmuscle Cell Signaling and Function J. Cell Biol., September 21, 1998; 142(6): 1395 - 1398. [Full Text] [PDF]

				B. Landolfi, S. Curci, L. Debellis, T. Pozzan, and A. M. Hofer Ca2+ Homeostasis in the Agonist-sensitive Internal Store: Functional Interactions Between Mitochondria and the ER Measured In Situ in Intact Cells J. Cell Biol., September 7, 1998; 142(5): 1235 - 1243. [Abstract] [Full Text] [PDF]

				C. Fasolato, P. Pizzo, and T. Pozzan Delayed Activation of the Store-operated Calcium Current Induced by Calreticulin Overexpression in RBL-1 Cells Mol. Biol. Cell, June 1, 1998; 9(6): 1513 - 1522. [Abstract] [Full Text]

				M. J. Barrero, M. Montero, and J. Alvarez Dynamics of [Ca2+] in the Endoplasmic Reticulum and Cytoplasm of Intact HeLa Cells. A COMPARATIVE STUDY J. Biol. Chem., October 31, 1997; 272(44): 27694 - 27699. [Abstract] [Full Text] [PDF]

				S. Arnaudeau, W. L. Kelley, J. V. Walsh Jr., and N. Demaurex Mitochondria Recycle Ca2+ to the Endoplasmic Reticulum and Prevent the Depletion of Neighboring Endoplasmic Reticulum Regions J. Biol. Chem., July 27, 2001; 276(31): 29430 - 29439. [Abstract] [Full Text] [PDF]