Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 383K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Albrecht, M. A. Articles by Friel, D. D. Search for Related Content PubMed PubMed Citation Articles by Albrecht, M. A. Articles by Friel, D. D. Social Bookmarking                            What's this?

Original Article

Attenuation of Endoplasmic Reticulum Ca²+ Accumulation at Low [Ca²+]_i during Weak Depolarization

Meredith A. Albrecht^a, Stephen L. Colegrove^a, Jarin Hongpaisan^b, Natalia B. Pivovarova^b, S. Brian Andrews^b, and David D. Friel^a

^a Department of Neuroscience, Case Western Reserve University, Cleveland, OH 44106
^b Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892
Department of Neuroscience, Case Western Reserve University, 10900 Euclid Ave. Cleveland, OH 44106.(216) 368-4650

ddf2{at}po.cwru.edu

Many cells express ryanodine receptors (RyRs) whose activation is thought to amplify depolarization-evoked elevations in cytoplasmic Ca²+ concentration ([Ca²+]_i) through a process of Ca²+-induced Ca²+ release (CICR). In neurons, it is usually assumed that CICR triggers net Ca²+ release from an ER Ca²+ store. However, since net ER Ca²+ transport depends on the relative rates of Ca²+ uptake and release via distinct pathways, weak activation of a CICR pathway during periods of ER Ca accumulation would have a totally different effect: attenuation of Ca²+ accumulation. Stronger CICR activation at higher [Ca²+]_i could further attenuate Ca²+ accumulation or trigger net Ca²+ release, depending on the quantitative properties of the underlying Ca²+ transporters. This and the companion study (Hongpaisan, J., N.B. Pivovarova, S.L. Colgrove, R.D. Leapman, and D.D. Friel, and S.B. Andrews. 2001. J. Gen. Physiol. 118:101–112) investigate which of these CICR "modes" operate during depolarization-induced Ca²+ entry in sympathetic neurons. The present study focuses on small [Ca²+]_i elevations (less than 350 nM) evoked by weak depolarization. The following two approaches were used: (1) Ca²+ fluxes were estimated from simultaneous measurements of [Ca²+]_i and I_Ca in fura-2–loaded cells (perforated patch conditions), and (2) total ER Ca concentrations ([Ca]_ER) were measured using X-ray microanalysis. Flux analysis revealed triggered net Ca²+ release during depolarization in the presence but not the absence of caffeine, and [Ca²+]_i responses were accelerated by SERCA inhibitors, implicating ER Ca²+ accumulation, which was confirmed by direct [Ca]_ER measurements. Ryanodine abolished caffeine-induced CICR and enhanced depolarization-induced ER Ca²+ accumulation, indicating that activation of the CICR pathway normally attenuates ER Ca²+ accumulation, which is a novel mechanism for accelerating evoked [Ca²+]_i responses. Theory shows how such a low gain mode of CICR can operate during weak stimulation and switch to net Ca²+ release at high [Ca²+]_i, a transition demonstrated in the companion study. These results emphasize the importance of the relative rates of Ca²+ uptake and release in defining ER contributions to depolarization-induced Ca²+ signals.

Key Words: calcium signaling • endoplasmic reticulum • caffeine • ryanodine • electron probe X-ray microanalysis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				G. Cui, B. E. Bernier, M. T. Harnett, and H. Morikawa Differential Regulation of Action Potential- and Metabotropic Glutamate Receptor-Induced Ca2+ Signals by Inositol 1,4,5-Trisphosphate in Dopaminergic Neurons J. Neurosci., April 25, 2007; 27(17): 4776 - 4785. [Abstract] [Full Text] [PDF]

				A. Verkhratsky Physiology and Pathophysiology of the Calcium Store in the Endoplasmic Reticulum of Neurons Physiol Rev, January 1, 2005; 85(1): 201 - 279. [Abstract] [Full Text] [PDF]

				N. N. Kasri, I. Sienaert, J. B. Parys, G. Callewaert, L. Missiaen, A. Jeromin, and H. De Smedt A Novel Ca2+-induced Ca2+ Release Mechanism in A7r5 Cells Regulated by Calmodulin-like Proteins J. Biol. Chem., July 18, 2003; 278(30): 27548 - 27555. [Abstract] [Full Text] [PDF]

				N. B. Pivovarova, L. D. Pozzo-Miller, J. Hongpaisan, and S. B. Andrews Correlated Calcium Uptake and Release by Mitochondria and Endoplasmic Reticulum of CA3 Hippocampal Dendrites after Afferent Synaptic Stimulation J. Neurosci., December 15, 2002; 22(24): 10653 - 10661. [Abstract] [Full Text] [PDF]

				M. A. Albrecht, S. L. Colegrove, and D. D. Friel Differential Regulation of ER Ca2+ Uptake and Release Rates Accounts for Multiple Modes of Ca2+-induced Ca2+ Release J. Gen. Physiol., March 1, 2002; 119(3): 211 - 233. [Abstract] [Full Text] [PDF]

				E. F. Barrett Contrasting Contributions of Endoplasmic Reticulum and Mitochondria to Ca2+ Handling in Neurons J. Gen. Physiol., July 1, 2001; 118(1): 79 - 82. [Full Text] [PDF]

				J. Hongpaisan, N. B. Pivovarova, S. L. Colegrove, R. D. Leapman, D. D. Friel, and S. B. Andrews Multiple Modes of Calcium-Induced Calcium Release in Sympathetic Neurons II: A [Ca2+]i- and Location-Dependent Transition from Endoplasmic Reticulum Ca Accumulation to Net Ca Release J. Gen. Physiol., July 1, 2001; 118(1): 101 - 112. [Abstract] [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents