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- Title
Presynaptic Ca<sub>V</sub>3.2 Channels Regulate Excitatory Neurotransmission in Nociceptive Dorsal Horn Neurons.
- Authors
Jacus, Megan O.; Uebele, Victor N.; Renger, John J.; Todorovic, Slobodan M.
- Abstract
It is generally accepted that presynaptic transmitter release is mainly regulated by subtypes of neuronal high-voltage-activated Ca2+ channels. Here for the first time, we examined the role of T-type Ca2+ 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.Wefound 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 CaV3.2 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.
- Subjects
NEUROTRANSMITTERS; CALCIUM channels; NEURAL transmission; NEURAL physiology; INTERNEURONS; NEUROPATHY; CELLULAR signal transduction; SYNAPSES
- Publication
Journal of Neuroscience, 2012, Vol 32, Issue 27, p9374
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0068-12.2012