Abstract
1. We have investigated whether receptors for ATP exist on neurones of the trigeminal mesencephalic nucleus (MNV) of the rat using whole-cell and outside-out patch-clamp recording in coronal brainstem slices. 2. With whole-cell recording, the batch application of ATP, adenosine 5'-O-[3-thiotriphosphate] (ATP gamma S) and alpha,beta methylene adenosine triphosphate (alpha beta meATP) caused concentration-dependent inward currents in all cells tested (holding potential, -62 mV), with EC50 values of 437, 15 and 254 microM, respectively. All three agonist-evoked currents developed rapidly (rise time, approximately 10-25 s), desensitized slowly (over approximately 20-50 s), cross-desensitized with each other, were associated with an increase in membrane conductance and were attenuated by the application of suramin (30 microM). 3. The inward current evoked by ATP decreased as the membrane potential was made less negative and had a zero current potential of +1.0 +/- 3.7 mV. The current-voltage relationship showed marked inward rectification. 4. Brief flickery single-channel openings could be resolved in response to ATP (3 microM) in outside-out membrane patches. Unitary current at -82 mV was -1.81 +/- 0.2 pA, which corresponds to a unitary conductance of 22 pS. 5. We conclude that proprioceptive MNV neurones contain ATP-gated cation channels. Such P2X purinoceptors may be involved in the processing of proprioceptive information, thus suggesting a potentially important physiological role of ATP.
MeSH Terms
Adenosine Triphosphate/physiology
Animals
Electrophysiology
In Situ Hybridization
In Vitro Techniques
Ion Channel Gating/physiology
Male
Membrane Potentials/physiology
Mesencephalon/cytology,metabolism,physiology
Neurons/metabolism,physiology
Patch-Clamp Techniques
Pons/cytology,metabolism,physiology
Proprioception/physiology
Rats
Rats, Wistar
Receptors, Purinergic P2/metabolism,physiology
Trigeminal Nuclei/cytology,metabolism,physiology
Chemicals
Receptors, Purinergic P2
Adenosine Triphosphate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Khakh B S
Department of Pharmacology, School of Medical Sciences, University Walk, University of Bristol, UK. b.s.khakh@bristol.ac.uk
Humphrey P P
Henderson G
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