P2X sub(7)-like receptor subunits enhance excitatory synaptic transmission at central synapses by presynaptic mechanisms

• Published in: Neuroscience 2004-01, Vol.128 (2), p.269-280
• Main Authors: Ireland, M F, Noakes, P G, Bellingham, M C
• Format: Article
• Language: English
• ISSN: 0306-4522
• DOI: 10.1016/j.neuroscience.2004.06.014

Recent studies demonstrate that P2X sub(7) receptor subunits (P2X sub(7)RS) are present at central and peripheral synapses and suggest that P2X sub(7)RS can regulate transmitter release. In brainstem slices from 15 to 26 day old pentobarbitone-anesthetized mice, we examined the effect of P2X sub(7)RS activation on excitatory postsynaptic currents (EPSCs) recorded from hypoglossal motoneurons using whole-cell patch clamp techniques. After blockade of most P2X receptors with suramin (which is inactive at P2X sub(7)RS) and of adenosine receptors with 8-phenyltheophylline (8PT), bath application of the P2X receptor agonist 3'-0-(4-benzoyl)ATP (BzATP) elicited a 40.5 plus or minus 16.0% (mean plus or minus S.E.M. n=8, P=0.039) increase in evoked EPSC amplitude and significantly reduced paired pulse facilitation of evoked EPSCs. This response to BzATP (with suramin and 8PT present) was completely blocked by prior application of Brilliant Blue G (200 nM or 2 mu M), a P2X sub(7)RS antagonist. In contrast, BzATP application with suramin and 8PT present did not alter miniature EPSC frequency or amplitude when action potentials were blocked with tetrodotoxin. These electrophysiological results suggest that P2X sub(7)RS activation increases central excitatory transmitter release via presynaptic mechanisms, confirming previous indirect measures of enhanced transmitter release. We suggest that possible presynaptic mechanisms underlying enhancement of evoked transmitter release by P2X sub(7)RS activation are modulation of action potential width or an increase in presynaptic terminal excitability, due to subthreshold membrane depolarization which increases the number of terminals releasing transmitter in response to stimulation.