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J Neurophysiol 88: 1212-1219, 2002;
0022-3077/02 $5.00
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The Journal of Neurophysiology Vol. 88 No. 3 September 2002, pp. 1212-1219
Copyright ©2002 by the American Physiological Society

Coexistence of Functional IP3 and Ryanodine Receptors in Vagal Sensory Neurons and Their Activation by ATP

Robert E. Hoesch,1 Katherine Yienger,1 Daniel Weinreich,2 and Joseph P. Y. Kao1

Medical Biotechnology Center, University of Maryland Biotechnology Institute,  1Department of Physiology and  2Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201

Hoesch, Robert E., Katherine Yienger, Daniel Weinreich, and Joseph P. Y. Kao. Coexistence of Functional IP3 and Ryanodine Receptors in Vagal Sensory Neurons and Their Activation by ATP. J. Neurophysiol. 88: 1212-1219, 2002. Intracellular photorelease of caged D-myo-inositol 1,4,5-trisphosphate (IP3), caffeine application, and immunofluorescence confocal microscopy were used to determine that D-myo-inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) coexist in rabbit vagal sensory nodose ganglion neurons (NGNs). ATP, an extracellular physiological signaling molecule, consistently evoked robust transient increases in cytosolic free Ca2+ concentration (Ca2+ transients). ATP applied in Ca2+-free physiological saline elicited Ca2+ transients that averaged approximately 70% of the amplitude of transients evoked in the presence of extracellular Ca2+. The component of the ATP-evoked Ca2+ transient that was independent of extracellular Ca2+ corresponds to Ca2+ release from intracellular stores. This release component was sensitive to the pharmacological antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), U73122, neomycin, and heparin (13.5-15 kD), indicating that P2 purinoreceptors (P2Y) and the IP3 signaling pathway are required for ATP-evoked Ca2+ release. Additionally, a portion of ATP-evoked Ca2+ release was inhibited by ryanodine, a selective blocker of RyRs. The ryanodine-insensitive component (approximately 70%) of ATP-evoked Ca2+ release corresponds to IP3-induced Ca2+ release via IP3Rs, while the ryanodine-sensitive component (approximately 30%) corresponds to consequent Ca2+-induced Ca2+ release (CICR) via RyRs. These results indicate that functional IP3Rs and RyRs coexist in nodose neurons and that both IP3-induced Ca2+ release and CICR can be activated by ATP.




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