HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by HORN, T. F. W. Articles by MacVICAR, B. A. Search for Related Content PubMed PubMed Citation Articles by HORN, T. F. W. Articles by MacVICAR, B. A.

Nitric oxide promotes intracellular calcium release from mitochondria in striatal neurons

THOMAS F. W. HORN¹, GERALD WOLF, STEVEN DUFFY, SAMUEL WEISS^*, GERBURG KEILHOFF and BRIAN A. MacVICAR^*

Institute for Medical Neurobiology, University of Magdeburg, Germany;
Department of Physiology, University of Alberta, Canada; and
^* Neuroscience Research Group, University of Calgary, Canada

¹Correspondence: Institute for Medical Neurobiology, University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany. E-mail: thomas.horn{at}medizin.uni-magdeburg.de

Overproduction of nitric oxide by NMDA receptor stimulation is implicated in calcium deregulation and neurodegeneration of striatal neurons. We investigated the involvement of nitric oxide (NO) in inducing intracellular calcium release and in modifying calcium transients evoked by NMDA. NO application (4–10 µM) reversibly and repeatedly increased the intracellular calcium concentration [Ca²⁺]_i in Fura-2- or fluo-3-loaded cultured mouse striatal neurons. NO-induced [Ca²⁺]_i responses persisted in the absence of extracellular calcium, indicating that Ca²⁺ was released from intracellular stores. The source of calcium was distinct from [Ca²⁺]_i-activated (ruthenium red and ryanodine sensitive) or IP₃-activated (thapsigargin-sensitive) Ca²⁺ stores and was not dependent on cGMP production because a cell permeant analog, 8-bromo-cGMP, did not increase basal [Ca²⁺]_i. Glucose removal potentiated the NO-induced release of [Ca²⁺]_i. In contrast, pretreatment with either the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone or cyclosporin A, a blocker of the mitochondrial permeability transition pore, prevented the [Ca²⁺]_i increase after NO. The rise in [Ca²⁺]_i during NO exposure was preceded by a decrease in mitochondrial membrane potential that was partly reversible during washout. Repeated applications of NMDA induced irreversible [Ca²⁺]_i responses in a subpopulation of striatal cells that were greatly reduced by the NOS inhibitor N-nitro-L-arginine. Calcium transients were prolonged by conjoint application of NMDA and NO. We conclude that NMDA-evoked [Ca²⁺]_i transients are modulated by endogenous NO production, which leads to release of calcium from the mitochondrial pool. An NO-activated mitochondrial permeability transition pore may lead to cell death after overstimulation of NMDA receptors.—Horn, T. F. W., Wolf, G., Duffy, S., Weiss, S., Keilhoff, G., MacVicar, B. A. Nitric oxide promotes intracellular calcium release from mitochondria in striatal neurons.

Key Words: nitric oxide synthase • NOS isoform • NMDA • NO production

This article has been cited by other articles:

				S. Wang, A. G. Teschemacher, J. F. R. Paton, and S. Kasparov Mechanism of nitric oxide action on inhibitory GABAergic signaling within the nucleus tractus solitarii FASEB J, July 1, 2006; 20(9): 1537 - 1539. [Abstract] [Full Text] [PDF]

				J. T. A. Meij, C. L. Haselton, K. L. Hillman, D. Muralikrishnan, M. Ebadi, and L. Yu Differential Mechanisms of Nitric Oxide- and Peroxynitrite-Induced Cell Death Mol. Pharmacol., October 1, 2004; 66(4): 1043 - 1053. [Abstract] [Full Text] [PDF]

				D.-P. Li, S.-R. Chen, T. F. Finnegan, and H.-L. Pan Signalling pathway of nitric oxide in synaptic GABA release in the rat paraventricular nucleus J. Physiol., January 1, 2004; 554(1): 100 - 110. [Abstract] [Full Text] [PDF]

				L. SCHILD, T. REINHECKEL, M. REISER, T. F. W. HORN, G. WOLF, and W. AUGUSTIN Nitric oxide produced in rat liver mitochondria causes oxidative stress and impairment of respiration after transient hypoxia FASEB J, December 1, 2003; 17(15): 2194 - 2201. [Abstract] [Full Text] [PDF]

				C. Chinopoulos, A. A. Starkov, and G. Fiskum Cyclosporin A-insensitive Permeability Transition in Brain Mitochondria: INHIBITION BY 2-AMINOETHOXYDIPHENYL BORATE J. Biol. Chem., July 18, 2003; 278(30): 27382 - 27389. [Abstract] [Full Text] [PDF]

				J. Chen, C. Wersinger, and A. Sidhu Chronic Stimulation of D1 Dopamine Receptors in Human SK-N-MC Neuroblastoma Cells Induces Nitric-oxide Synthase Activation and Cytotoxicity J. Biol. Chem., July 18, 2003; 278(30): 28089 - 28100. [Abstract] [Full Text] [PDF]

				I. C. Gerling, Y. Sun, R. A. Ahokas, L. A. Wodi, S. K. Bhattacharya, K. J. Warrington, A. E. Postlethwaite, and K. T. Weber Aldosteronism: an immunostimulatory state precedes proinflammatory/fibrogenic cardiac phenotype Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H813 - H821. [Abstract] [Full Text] [PDF]