The Journal of Neurophysiology Vol. 77 No. 5 May 1997, pp. 2573-2584
Copyright ©1997 The American Physiological Society

Activation of Ca²⁺-Dependent Currents in Dorsal Root Ganglion Neurons by Metabotropic Glutamate Receptors and Cyclic ADP-Ribose Precursors

Jane H. Crawford¹, John F. Wootton², Guy R. Seabrook¹, and Roderick H. Scott³

¹ Merck Sharp and Dohme, Neuroscience Research Centre, Harlow, Essex CM20 2QR, United Kingdom; ² Department of Physiology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-601; and ³ Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom

Crawford, Jane H., John F. Wootton, Guy R. Seabrook, and Roderick H. Scott. Activation of Ca²⁺-dependent currents in dorsal root ganglion neurons by metabotropic glutamate receptors and cyclic ADP-ribose precursors. J. Neurophysiol. 77: 2573-2584, 1997. Cultured dorsal root ganglion neurons were voltage clamped at 90 mV to study the effects of intracellular application of nicotinamide adenine dinucleotide (NAD⁺), intracellular flash photolysis of caged 3,5-cyclic guanosine monophosphate (cGMP), and metabotropic glutamate receptor activation. The activation of metabotropic glutamate receptors evoked inward Ca²⁺-dependent currents in most cells. This was mimicked both by intracellular flash photolysis of the caged axial isomer of cGMP [P-1-(2-nitrophenyl)ethyl cGMP] and intracellular application of NAD⁺. Whole cell Ca²⁺-activated inward currents were used as a physiological index of raised intracellular Ca²⁺ levels. Extracellular application of 10 µM glutamate evoked the activation of Ca²⁺-dependent inward currents, thus reflecting a rise in intracellular Ca²⁺ levels. Similar inward currents were also activated after isolation of metabotropic glutamate receptor activation by application of 10 µM glutamate in the presence of 20 µM 6-cyano-7-nitroquinoxaline-2,3-dione and 20 µM dizocilpine maleate (MK 801), or by extracellular application of 10 µM trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid. Intracellular photorelease of cGMP, from its caged axial isomer, in the presence of NAD⁺ was also able to evoke similar Ca²⁺-dependent inward currents. Intracellular application of NAD⁺ alone produced a concentration-dependent effect on inward current activity. Responses to both metabotropic glutamate receptor activation and cGMP were suppressed by intracellular ryanodine, chelation of intracellular Ca²⁺ by bis-(o-aminophenoxy)-N,N,N,N-tetraacetic acid, and depletion of intracellular Ca²⁺ stores, but were insensitive to the removal of extracellular Ca²⁺. Therefore both cGMP, possibly via a mechanism that involves NAD⁺ and/or cyclic ADP-ribose, and glutamate can mobilize intracellular Ca²⁺ from ryanodine-sensitive stores in sensory neurons.

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