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) All Versions of this Article: 288/1/C204    most recent 00330.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 ISI Web of Science (23) Citing Articles via Google Scholar Google Scholar Articles by Mongin, A. A. Articles by Kimelberg, H. K. Search for Related Content PubMed PubMed Citation Articles by Mongin, A. A. Articles by Kimelberg, H. K.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

ATP regulates anion channel-mediated organic osmolyte release from cultured rat astrocytes via multiple Ca²⁺-sensitive mechanisms

¹Center for Neuropharmacology and Neuroscience, Albany Medical College, and ²Ordway Research Institute, Albany, New York

Submitted 8 July 2004 ; accepted in final form 8 September 2004

Ubiquitously expressed volume-regulated anion channels (VRACs) are activated in response to cell swelling but may also show limited activity in nonswollen cells. VRACs are permeable to inorganic anions and small organic osmolytes, including the amino acids aspartate, glutamate, and taurine. Several recent reports have demonstrated that neurotransmitters or hormones, such as ATP and vasopressin, induce or strongly potentiate astrocytic whole cell Cl^– currents and amino acid release, which are inhibited by VRAC blockers. In the present study, we explored the intracellular signaling mechanisms mediating the effects of ATP on D-[³H]aspartate release via the putative VRAC pathway in rat primary astrocyte cultures. Cells were exposed to moderate (5%) or substantial (30%) reductions in medium osmolarity. ATP strongly potentiated D-[³H]aspartate release in both moderately swollen and substantially swollen cells. These ATP effects were blocked (80% inhibition) by intracellular Ca²⁺ chelation with BAPTA-AM, calmodulin inhibitors, or a combination of the inhibitors of protein kinase C (PKC) and calmodulin-dependent kinase II (CaMK II). In contrast, control D-[³H]aspartate release activated by the substantial hyposmotic swelling showed little (25% inhibition) sensitivity to the same pharmacological agents. These data indicate that ATP regulates VRAC activity via two separate Ca²⁺-sensitive signaling cascades involving PKC and CaMK II and that cell swelling per se activates VRACs via a separate Ca²⁺/calmodulin-independent signaling mechanism. Ca²⁺-dependent organic osmolyte release via VRACs may contribute to the physiological functions of these channels in the brain, including astrocyte-to-neuron intercellular communication.

volume-regulated anion channels; protein kinase C; calcium/calmodulin-dependent kinase II; glutamate release; neuron-glia communication

This article has been cited by other articles:

				A. Salin-Cantegrel, M. Shekarabi, S. Holbert, P. Dion, D. Rochefort, J. Laganiere, S. Dacal, P. Hince, L. Karemera, C. Gaspar, et al. HMSN/ACC truncation mutations disrupt brain-type creatine kinase-dependant activation of K+/Cl- co-transporter 3 Hum. Mol. Genet., September 1, 2008; 17(17): 2703 - 2711. [Abstract] [Full Text] [PDF]

				M. B. Friis, K. G. Vorum, and I. H. Lambert Volume-sensitive NADPH oxidase activity and taurine efflux in NIH3T3 mouse fibroblasts Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1552 - C1565. [Abstract] [Full Text] [PDF]

				D. J. Foster, A. M. Heacock, R. F. Keep, and S. K. Fisher Activation of Muscarinic Cholinergic Receptors on Human SH-SY5Y Neuroblastoma Cells Enhances Both the Influx and Efflux of K+ under Conditions of Hypo-Osmolarity J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 457 - 465. [Abstract] [Full Text] [PDF]

				T. A. Cheema and S. K. Fisher Cholesterol Regulates Volume-Sensitive Osmolyte Efflux from Human SH-SY5Y Neuroblastoma Cells following Receptor Activation J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 648 - 657. [Abstract] [Full Text] [PDF]

				S. N. Orlov and A. A. Mongin Salt-sensing mechanisms in blood pressure regulation and hypertension Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2039 - H2053. [Abstract] [Full Text] [PDF]

				I. Morales, J. G. Dopico, M. Sabate, T. Gonzalez-Hernandez, and M. Rodriguez Substantia nigra osmoregulation: taurine and ATP involvement Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1934 - C1941. [Abstract] [Full Text] [PDF]

				G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]

				S. J. Mulligan and B. A. MacVicar VRACs CARVe a Path for Novel Mechanisms of Communication in the CNS Sci. Signal., October 17, 2006; 2006(357): pe42 - pe42. [Abstract] [Full Text] [PDF]

				I. F. Abdullaev, A. Rudkouskaya, G. P. Schools, H. K. Kimelberg, and A. A. Mongin Pharmacological comparison of swelling-activated excitatory amino acid release and Cl- currents in cultured rat astrocytes J. Physiol., May 1, 2006; 572(3): 677 - 689. [Abstract] [Full Text] [PDF]

				T. A. Cheema, C. E. Ward, and S. K. Fisher Subnanomolar Concentrations of Thrombin Enhance the Volume-Sensitive Efflux of Taurine from Human 1321N1 Astrocytoma Cells J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 755 - 763. [Abstract] [Full Text] [PDF]

				A. Charles Reaching Out Beyond the Synapse: Glial Intercellular Waves Coordinate Metabolism Sci. Signal., February 8, 2005; 2005(270): pe6 - pe6. [Abstract] [Full Text] [PDF]