Nerve injury alters profile of receptor-mediated Ca2+ channel modulation in vagal afferent neurons of rat nodose ganglia.
Although nerve injury is known to up- and down-regulate some metabotropic receptors in vagal afferent neurons of the nodose ganglia (NG), the functional significance has not been elucidated. In the present study, thus, we examined whether nerve injury affected receptor-mediated Ca2+ channel modulation in the NG neurons. In this regard, unilateral vagotomy was performed using male Sprague-Dawley rats. One week after vagotomy, Ca2+ currents were recorded using the whole-cell variant of patch-clamp technique in enzymatically dissociated NG neurons. In sham controls, norepinephrine (NE)-induced Ca2+ current inhibition was negligible. Following vagotomy, however, the NE responses were dramatically increased. This phenomenon was in accordance with up-regulation of alpha2A/B-adrenergic receptor mRNAs as quantified using real-time RT-PCR analysis. In addition, neuropeptide Y (NPY) and prostaglandin E2 responses were moderately augmented in vagotomized NG neurons. The altered NPY response appears to be caused by up-regulation of Y2 receptors negatively coupled to Ca2+ channels. In contrast, nerve injury significantly suppressed opioid (tested with DAMGO)-induced Ca2+ current inhibition with down-regulation of micro-receptors. Taken together, these results demonstrated for the first time that the profile of neurotransmitter-induced Ca2+ channel modulation is significantly altered in the NG neurons under pathophysiological state of nerve injury.
Huang
Xue-Zhu
XZ
Department of Physiology, Institute of Basic Medical Science, Yonsei University Wonju College of Medicine, Ilsan-Dong 162, Wonju, Kangwon-Do 220-701, South Korea.
Won
Yu-Jin
YJ
Park
Byong-Gon
BG
Cho
Byung Pil
BP
Lee
Joong-Woo
JW
Jeong
Seong-Woo
SW
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009475:Neurons, Afferent / Q000473:pathology / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism; D009620:Nodose Ganglion / Q000293:injuries / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014628:Vagotomy
C547770:Adra2a protein, rat; C547773:Adra2b protein, rat; D015220:Calcium Channels; D009478:Neuropeptide Y; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D015232:Dinoprostone