Distinct ATP-activated currents in different types of neurons dissociated from rat dorsal root ganglion Chaoying Li a, *, Robert W. Peoples a , Thomas H. Lanthorn b , Zhi-Wang Li c , Forrest F. Weight a a Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-8115, USA b Department of Cell Biology, Astra Arcus USA, 755 Jefferson Road, Rochester, NY 14534, USA c Department of Molecular and Cellular Neurobiology, Research Center of Experimental Medicine, Tongji Medical University, Wuhan 430030, People’s Republic of China Received 2 December 1998; received in revised form 25 January 1999; accepted 25 January 1999 Abstract Rat dorsal root ganglion neurons can be classified into at least three distinct groups based on cell size, afferent fiber diameter, electrophysiological properties, sensitivity to vanilloid agonists such as capsaicin, and function. In the present study, ATP- activated current in these neurons was characterized using whole-cell patch-clamp recording. Small diameter (30 mm) cells had high capsaicin sensitivity, high affinity for ATP, and rapidly desensitizing ATP-activated current. Medium diameter (30–50 mm) cells had no capsaicin sensitivity, lower affinity for ATP and slowly desensitizing ATP-activated current. Large diameter (50 mm) cells were insensitive to both capsaicin and ATP. These findings suggest that distinct types of ATP receptor-ion channels are expressed in different types of dorsal root ganglion neurons, and may contribute to the functional differences among these types of neurons.  1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Adenosine 5′-triphosphate; Receptor; Neuron; Dorsal root ganglion; Ion channel; P2X purinoceptor; Capsaicin Extracellular adenosine 5′-triphosphate (ATP) has been reported to produce excitatory actions in the nervous sys- tem, such as excitatory postsynaptic potentials or currents in both central [1,8] and peripheral [9,17] neurons and excita- tory junction potentials in smooth muscle cells [18], via activation of a class of ATP-gated membrane ion channels designated P2X receptors. Activation of P2X receptors at negative membrane potentials induces an inward ion cur- rent, which shows inward rectification, non-selective cation permeability and a reversal potential close to 0 mV. Among various tissues and cell types, however, differences in the effect of cations [5,13,14] current-voltage relationships, agonist selectivity, and desensitization [11] of ATP-acti- vated current have been observed, as might be predicted by the existence of multiple subtypes of P2X receptor-chan- nels [19]. For instance, in rat nodose ganglion neurons, there are at least two types of ATP-activated currents which differ in desensitization and modulation by endogenous agents: one type exhibits slight to moderate desensitization, and is markedly enhanced by extracellular Zn 2 + , Cu 2 + and pro- tons, while another type exhibits rapid desensitization, and is insensitive to Zn 2 + , Cu 2 + and protons [13,14]. In addition, two distinct ATP-activated currents, transient and persis- tent, have been reported in nociceptors of rat trigeminal ganglion neurons [5,6]. In the present study, we found two types of ATP-activated current in adult rat dorsal root gang- lion (DRG) neurons, which have distinct distributions in these neurons. Acute dissociation of neurons from the DRG of male Sprague–Dawley rats (250–350 g) and whole-cell patch- clamp recording from these neurons were performed as described previously for nodose ganglion neurons [13]. Ani- mal care and use in this study was approved by the NIAAA Animal Care and Use Committee (protocol LMCN-SP-05) in accordance with NIH guidelines. Membrane potential Neuroscience Letters 263 (1999) 57–60 0304-3940/99/$ - see front matter  1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3940(99)00114-7 * Corresponding author. Department of Cell Biology, Astra Arcus USA, Three Biotech, One Innovation Dr., Worcester, MA 01615, USA. Tel.: +508-4213578; fax: +508-4213553; e-mail: chaoying.li@arcus.us.astra.com