期刊
PAIN
卷 116, 期 3, 页码 194-204出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/j.pain.2005.04.002
关键词
CGRP; CGRP receptor; DRG neurons; TTX-R Na+ current; protein kinase A; protein kinase C
The neuropeptide calcitonin gene-related peptide (CGRP) binds to a subpopulation of dorsal root ganglion (DRG) neurons, elevates intracellular calcium, and causes inward currents in about 30% of lumbar DRG neurons. Using whole-cell patch clamp recordings, we found in the present study that application of CGRP to isolated and cultured DRG neurons from the adult rat enhances voltage-gated TTX-resistant (TTX-R) Na+ inward currents in about 30% of small- to medium-sized DRG neurons. During CGRP, peak densities of Na+ currents increased significantly. CGRP shifted the membrane conductance of the CGRP-responsive cells towards hyperpolarization without changing the slope of the peak conductance curve. The effect of CGRP was blocked by coadministration of CGRP(8-37), an antagonist at the CGRP receptor. The effect of CGRP was also blocked after bath application of PKA(14-22), a membrane-permeant blocker of protein kinase A, and PKC19-31, a PKC inhibitor, in the recording pipette. These data show pronounced facilitatory effects of CGRP on TTX-R Na+ currents in DRG neurons which are mediated through CGRP receptors and intracellular pathways involving protein kinases A and C. Thus, in addition to prostaglandins, CGRP is another mediator that affects TTX-R Na+ currents which are thought to occur mainly in nociceptive DRG neurons. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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