TRPV1 receptor mediates glutamatergic synaptic input to dorsolateral periaqueductal gray (dl-PAG) neurons.
The purpose of this study was to determine the role of transient receptor potential vanilloid type 1 (TRPV1) receptor in modulating neuronal activity of the dorsolateral periaqueductal gray (dl-PAG) through excitatory and inhibitory synaptic inputs. First, whole cell voltage-clamp recording was performed to obtain the spontaneous miniature excitatory postsynaptic currents (mEPSCs) and inhibitory postsynaptic currents (mIPSCs) of the dl-PAG neurons. As 1 microM of capsaicin was applied into the perfusion chamber, the frequency of mEPSCs was increased from 3.21 +/- 0.49 to 5.64 +/- 0.64 Hz (P < 0.05, n = 12) without altering the amplitude and the decay time constant of mEPSCs. In contrast, capsaicin had no distinct effect on mIPSCs. A specific TRPV1 receptor antagonist, iodo-resiniferatoxin (i-RTX, 300 nM), decreased the frequency of mEPSCs from 3.51 +/- 0.29 to 2.01 +/- 0.2 Hz (P < 0.05, n = 8) but did not alter the amplitude and decay time. In addition, i-RTX applied into the chamber abolished the effect of capsaicin on mEPSC of the dl-PAG. In another experiment, spontaneous action potential of the dl-PAG neurons was recorded using whole cell current-clamp methods. Capsaicin significantly elevated the discharge rate of the dl-PAG neurons from 3.03 +/- 0.38 to 5.96 +/- 0.87 Hz (n = 8). The increased firing activity was abolished in the presence of glutamate N-methy-D-aspartate (NMDA) and non-NMDA antagonists, 2-amino-5-phosphonopentanoic acid, and 6-cyano-7-nitroquinoxaline-2,3-dione. The results from this study provide the first evidence indicating that activation of TRPV1 receptors increases the neuronal activity of the dl-PAG through selective potentiation of glutamatergic synaptic inputs.
Xing
Jihong
J
Heart and Vascular Institute and Department of Medicine, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.
Li
Jianhua
J
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D017776:Autonomic Pathways / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002211:Capsaicin / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004224:Diterpenes; D018691:Excitatory Amino Acid Antagonists; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C468130:iodoresiniferatoxin; D018698:Glutamic Acid; D002211:Capsaicin