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MCP-1 enhances excitability of nociceptive neurons in chronically compressed dorsal root ganglia.
J Neurophysiol. 2006 Nov; 96(5):2189-99.JN

Abstract

Previous experimental results from our laboratory demonstrated that monocyte chemoattractant protein-1 (MCP-1) depolarizes or increases the excitability of nociceptive neurons in the intact dorsal root ganglion (DRG) after a chronic compression of the DRG (CCD), an injury that upregulates neuronal expression of both MCP-1 and mRNA for its receptor CCR2. We presently explore the ionic mechanisms underlying the excitatory effects of MCP-1. MCP-1 (100 nM) was applied, after CCD, to acutely dissociated small DRG neurons with nociceptive properties. Under current clamp, the proportion of neurons depolarized was similar to that previously observed for CCD-treated neurons in the intact ganglion, although the magnitude of depolarization was greater. MCP-1 induced a decrease in rheobase by 44 +/- 10% and some cells became spontaneously active at resting potential. Action potential width at a voltage equal to 10% of the peak height was increased from 4.94 +/- 0.23 to 5.90 +/- 0.47 ms. In voltage clamp, MCP-1 induced an inward current in 27 of 50 neurons held at -60 mV, which increased with concentration over the range of 3 to 300 nM (EC(50) = 45 nM). The MCP-1-induced current was not voltage dependent and had an estimated reversal potential of -27 mV. In addition, MCP-1 inhibited a voltage-dependent, noninactivating outward current, presumably a delayed rectifier type K(+) conductance. We conclude that MCP-1 enhances excitability in CCD neurons by, at least, two mechanisms: 1) activation of a nonvoltage-dependent depolarizing current with characteristics similar to a nonselective cation conductance and 2) inhibition of a voltage-dependent outward current.

Authors+Show Affiliations

Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06510, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16775210

Citation

Sun, J H., et al. "MCP-1 Enhances Excitability of Nociceptive Neurons in Chronically Compressed Dorsal Root Ganglia." Journal of Neurophysiology, vol. 96, no. 5, 2006, pp. 2189-99.
Sun JH, Yang B, Donnelly DF, et al. MCP-1 enhances excitability of nociceptive neurons in chronically compressed dorsal root ganglia. J Neurophysiol. 2006;96(5):2189-99.
Sun, J. H., Yang, B., Donnelly, D. F., Ma, C., & LaMotte, R. H. (2006). MCP-1 enhances excitability of nociceptive neurons in chronically compressed dorsal root ganglia. Journal of Neurophysiology, 96(5), 2189-99.
Sun JH, et al. MCP-1 Enhances Excitability of Nociceptive Neurons in Chronically Compressed Dorsal Root Ganglia. J Neurophysiol. 2006;96(5):2189-99. PubMed PMID: 16775210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MCP-1 enhances excitability of nociceptive neurons in chronically compressed dorsal root ganglia. AU - Sun,J H, AU - Yang,B, AU - Donnelly,D F, AU - Ma,C, AU - LaMotte,R H, Y1 - 2006/06/14/ PY - 2006/6/16/pubmed PY - 2006/12/9/medline PY - 2006/6/16/entrez SP - 2189 EP - 99 JF - Journal of neurophysiology JO - J Neurophysiol VL - 96 IS - 5 N2 - Previous experimental results from our laboratory demonstrated that monocyte chemoattractant protein-1 (MCP-1) depolarizes or increases the excitability of nociceptive neurons in the intact dorsal root ganglion (DRG) after a chronic compression of the DRG (CCD), an injury that upregulates neuronal expression of both MCP-1 and mRNA for its receptor CCR2. We presently explore the ionic mechanisms underlying the excitatory effects of MCP-1. MCP-1 (100 nM) was applied, after CCD, to acutely dissociated small DRG neurons with nociceptive properties. Under current clamp, the proportion of neurons depolarized was similar to that previously observed for CCD-treated neurons in the intact ganglion, although the magnitude of depolarization was greater. MCP-1 induced a decrease in rheobase by 44 +/- 10% and some cells became spontaneously active at resting potential. Action potential width at a voltage equal to 10% of the peak height was increased from 4.94 +/- 0.23 to 5.90 +/- 0.47 ms. In voltage clamp, MCP-1 induced an inward current in 27 of 50 neurons held at -60 mV, which increased with concentration over the range of 3 to 300 nM (EC(50) = 45 nM). The MCP-1-induced current was not voltage dependent and had an estimated reversal potential of -27 mV. In addition, MCP-1 inhibited a voltage-dependent, noninactivating outward current, presumably a delayed rectifier type K(+) conductance. We conclude that MCP-1 enhances excitability in CCD neurons by, at least, two mechanisms: 1) activation of a nonvoltage-dependent depolarizing current with characteristics similar to a nonselective cation conductance and 2) inhibition of a voltage-dependent outward current. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/16775210/MCP_1_enhances_excitability_of_nociceptive_neurons_in_chronically_compressed_dorsal_root_ganglia_ L2 - https://journals.physiology.org/doi/10.1152/jn.00222.2006?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -