Calcitonin gene-related peptide enhances TTX-resistant sodium currents in cultured dorsal root ganglion neurons from adult rats.
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.
Natura
Gabriel
G
Institut für Physiologie, University of Jena, Teichgraben 8, D-07740 Jena, Germany.
von Banchet
Gisela Segond
GS
Schaible
Hans-Georg
HG
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010446:Peptide Fragments / Q000494:pharmacology; D011493:Protein Kinase C / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology*; D013997:Time Factors
D000779:Anesthetics, Local; D010446:Peptide Fragments; D015222:Sodium Channels; C073885:protein kinase C (19-31); D013779:Tetrodotoxin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D015740:Calcitonin Gene-Related Peptide