Multiple actions of 1S,3R-ACPD in modulating endogenous synaptic transmission to spinal respiratory motoneurons.
To determine physiological roles of metabotropic glutamate receptors (mGluRs) affecting breathing, we examined the effects of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) on synaptic transmission and excitability of phrenic motoneurons (PMNs) in an in vitro neonatal rat brainstem/spinal cord preparation. The effects of 1S,3R-ACPD were multiple, including reduction of inspiratory-modulated synaptic currents and increase of neuronal excitability via an inward current (Iacpd) associated with a decrease of membrane conductance. The mechanism underlying synaptic depression was examined. We found that 1S,3R-ACPD reduced the frequency but not the amplitude of miniature excitatory postsynaptic currents. The current induced by exogenous AMPA was not significantly affected by 1S,3R-ACPD. These results suggest that 1S,3R-ACPD-induced reduction of inspiratory synaptic currents is mediated by presynaptic mGluRs. We also examined the ionic basis for Iacpd. We found that Iacpd had a reversal potential of approximately -100 mV, close to the estimated, EK+ (-95 mV). Elevating extracellular [K+] to 9 mM reduced the Iacpd reversal potential to -75 mV. The K+ channel blocker Ba2+ induced an inward current with a reversal potential at -93 mV associated with a decrease of membrane conductance, closely resembling the effect of 1S,3R-ACPD. Moreover, Ba2+, occluded 1S,3R-ACPD effects. In the presence of Ba2+, Iacpd and the 1S,3R-ACPD-induced decrease of membrane conductance were diminished. Our data indicate that the dominant component of Iacpd results from the blockade of a Ba(2+)-sensitive resting K+ conductance. We conclude that the activation of mGluRs affects the inspiratory-modulated activity of PMNs via distinct mechanisms at pre- and postsynaptic sites.
Dong
X W
XW
Department of Physiological Science, University of California at Los Angeles 90095-1527, USA.
Morin
D
D
Feldman
J L
JL
D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004553:Electric Conductivity; D009046:Motor Neurons / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology* / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
D009498:Neurotoxins; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane