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Pre‐ and postsynaptic contributions of voltage‐dependent Ca 2+ channels to nociceptive transmission in rat spinal lamina I neurons
Author(s) -
Heinke B.,
Balzer E.,
Sandkühler J.
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.03083.x
Subject(s) - cnqx , postsynaptic potential , channel blocker , chemistry , neuroscience , nociception , voltage dependent calcium channel , ampa receptor , neurotransmission , nmda receptor , excitatory postsynaptic potential , biophysics , pharmacology , inhibitory postsynaptic potential , medicine , receptor , calcium , biology , biochemistry , organic chemistry
Activation of voltage‐dependent Ca 2+ channels (VDCCs) is critical for neurotransmitter release, neuronal excitability and postsynaptic Ca 2+ signalling. Antagonists of VDCCs can be antinociceptive in different animal pain models. Neurons in lamina I of the spinal dorsal horn play a pivotal role in the processing of pain‐related information, but the role of VDCCs to the activity‐dependent Ca 2+ increase in lamina I neurons and to the synaptic transmission between nociceptive afferents and second order neurons in lamina I is not known. This has now been investigated in a lumbar spinal cord slice preparation from young Sprague–Dawley rats. Microfluorometric Ca 2+ measurements with fura‐2 have been used to analyse the Ca 2+ increase in lamina I neurons after depolarization of the cells, resulting in a distinct and transient increase of the cytosolic Ca 2+ concentration. This Ca 2+ peak was reduced by the T‐type channel blocker, Ni 2+ , by the L‐type channel blockers, nifedipine and verapamil, and by the N‐type channel blocker, ω‐conotoxin GVIA. The P/Q‐type channel antagonist, ω‐agatoxin TK, had no effect on postsynaptic [Ca 2+ ] i . The NMDA receptor channel blocker D‐AP5 reduced the Ca 2+ peak, whereas the AMPA receptor channel blocker CNQX had no effect. Postsynaptic currents, monosynaptically evoked by electrical stimulation of the attached dorsal roots with C‐fibre and Aδ‐fibre intensity, respectively, were reduced by N‐type channel blocker ω‐conotoxin GVIA and to a much lesser extent, by P/Q‐type channel antagonist ω‐agatoxin TK, and the L‐type channel blockers verapamil, respectively. No difference was found between unidentified neurons and neurons projecting to the periaqueductal grey matter. This is the first quantitative description of the relative contribution of voltage‐dependent Ca 2+ channels to the synaptic transmission in lamina I of the spinal dorsal horn, which is essential in the processing of pain‐related information in the central nervous system.