title: Presynaptic Cav3.2 channels regulate excitatory neurotransmission in nociceptive dorsal horn neurons.
abstract: It is generally accepted that presynaptic transmitter release is mainly regulated by subtypes of neuronal high-voltage-activated Ca(2+) channels. Here for the first time, we examined the role of T-type Ca(2+) channels (T-channels) in synaptic transmission in the dorsal horn (DH) of the spinal cord using patch-clamp recordings from acute spinal cord preparations from both rat and mouse. We found that selective pharmacological antagonism of T-channels inhibited spontaneous synaptic release of glutamate in superficial laminae I-II of the DH, while GABA release was spared. We found similar effect in identified nociceptive projection neurons of lamina I of the DH, but not in inhibitory DH interneurons. In comparison, antagonism of T-channels did not affect excitatory transmission in deeper non-nociceptive DH laminae. Furthermore, we used isoform-specific agents, knock-out mice and immunohistochemistry to specifically implicate presynaptic Ca(V)3.2 channels. We also used an animal model of painful diabetic neuropathy to demonstrate that blocking T-channels in superficial DH neurons suppressed spontaneous excitatory synaptic transmission in diabetic rats in greater degree than in healthy age-matched animals. These studies provide previously unknown information regarding the role of presynaptic T-channels in nociceptive signaling in the spinal cord.
authors: Department of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
authors: Megan O
authors: MO
authors: Jacus
authors: Victor N
authors: VN
authors: Uebele
authors: John J
authors: JJ
authors: Renger
authors: Slobodan M
authors: SM
authors: Todorovic
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000502:physiology*; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009619:Nociceptors / Q000473:pathology / Q000502:physiology*; D009924:Organ Culture Techniques; D020671:Posterior Horn Cells / Q000473:pathology / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: C504883:Cacna1h protein, mouse; C509958:Cacna1h protein, rat; D020747:Calcium Channels, T-Type