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ATP facilitates spontaneous glycinergic IPSC frequency at dissociated rat dorsal horn interneuron synapses.
- Source :
-
The Journal of physiology [J Physiol] 2000 Apr 15; Vol. 524 Pt 2, pp. 471-83. - Publication Year :
- 2000
-
Abstract
- 1. The ATP action on spontaneous miniature glycinergic inhibitory postsynaptic currents (mIPSCs) was investigated in rat substantia gelatinosa (SG) neurons mechanically dissociated from the 2nd layer of the dorsal horn in which their presynaptic glycinergic nerve terminals remained intact. 2. ATP reversibly facilitated the frequency of the mIPSCs in a concentration-dependent manner without affecting their amplitude distribution. The ATP agonist, 2-methylthioATP (2MeSATP), mimicked the ATP action, while another ATP receptor agonist, alphabeta-methylene-ATP (alpha,beta-meATP), had no effect on mIPSCs. 3. The ATP receptor antagonists, suramin (1 x 10-6 M) and pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (1 x 10-5 M), completely blocked the facilitatory effect of ATP on glycine release (102.0 +/- 11.2 % and 99.3 +/- 16.2 %, n = 6, respectively) without altering the current amplitude distributions. 4. N-Ethylmaleimide (NEM), a sulphydryl alkylating agent, suppressed the inhibitory effect of adenosine on mIPSC frequency (111.2 +/- 13. 3 %, n = 4) without altering the current amplitude distribution. However, ATP still facilitated the mIPSC frequency (693.3 +/- 245.2 %, n = 4) even in the presence of NEM. 5. The facilitatory effect of ATP (1 x 10-5 M) on mIPSC frequency was not affected by adding 1 x 10-4 M Cd2+ to normal external solution but was eliminated in a Ca2+-free external solution. 6. These results suggest that ATP enhances glycine release from nerve terminals, presumably resulting in the inhibition of SG neurons which conduct nociceptive signals to the CNS. This presynaptic P2X-type ATP receptor may function to prevent excess excitability in SG neurons, thus preventing an excessive pain signal and/or SG cell death.
- Subjects :
- Adenosine Triphosphate agonists
Adenosine Triphosphate pharmacology
Animals
Calcium physiology
Electrophysiology
Ethylmaleimide pharmacology
Excitatory Postsynaptic Potentials drug effects
In Vitro Techniques
Interneurons drug effects
Membrane Potentials drug effects
Membrane Potentials physiology
Patch-Clamp Techniques
Posterior Horn Cells drug effects
Purinergic P2 Receptor Agonists
Purinergic P2 Receptor Antagonists
Rats
Rats, Wistar
Receptors, Glycine drug effects
Receptors, Glycine physiology
Receptors, Presynaptic drug effects
Synapses drug effects
Adenosine Triphosphate physiology
Excitatory Postsynaptic Potentials physiology
Glycine physiology
Interneurons physiology
Posterior Horn Cells physiology
Synapses physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3751
- Volume :
- 524 Pt 2
- Database :
- MEDLINE
- Journal :
- The Journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 10766927
- Full Text :
- https://doi.org/10.1111/j.1469-7793.2000.t01-1-00471.x