Calcitonin gene-related peptide enhances TTX-resistant... : PAIN (original) (raw)
Article
Calcitonin gene-related peptide enhances TTX-resistant sodium currents in cultured dorsal root ganglion neurons from adult rats
Institut für Physiologie, University of Jena, Teichgraben 8, D-07740 Jena, Germany
*Corresponding author. Tel.: +49 3641 938810; fax: +49 3641 938812.
E-mail address:[email protected]
Received 28 October 2004; received in revised form 11 March 2005; accepted 4 April 2005.
Abstract
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 CGRP8–37, an antagonist at the CGRP receptor. The effect of CGRP was also blocked after bath application of PKA14–22, 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.
© 2005 Lippincott Williams & Wilkins, Inc.