Mutual occlusion of P2X ATP receptors and nicotinic receptors on sympathetic neurons of the guinea-pig
Corresponding author E. M. Silinsky: Department of Molecular Pharmacology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA. Email: firstname.lastname@example.org
- 1The interaction of ion channels activated by nicotinic receptor agonists with ion channels gated by extracellular ATP (i.e. P2X receptors) was studied on sympathetic neurons acutely dissociated from coeliac ganglia of the guinea-pig. Patch clamp methods were used to measure the inward current generated through these non-selective cationic channels under voltage clamp.
- 2At the whole cell level, the specific nicotinic receptor agonists nicotine (5-100 μM) or cytisine (50-75 μM) and the P2X receptor agonists ATP (0.1-7 μM) or α,β-methylene ATP (6 μM) were examined separately and in the presence of the other receptor activator. When a nicotinic and P2X receptor agonist were applied together, mutually occlusive effects were generally observed. This occurred even with concentrations of agonists that in themselves generated little to no inward current.
- 3The occlusive effects of nicotinic agonists on ATP-gated currents were blocked by the nicotinic receptor/ion channel blocker hexamethonium (150 μM). The occlusive effects of ATP analogues on inward currents generated by nicotinic agonists were blocked by the P2X receptor antagonist suramin (100 μM).
- 4Mutual occlusion of the effects of nicotinic agonists and ATP analogues were also observed when currents through single channels were studied in excised (outside-out) patches.
- 5The results suggest that nicotinic receptors and P2X ATP receptors do not act independently in these sympathetic neurons.