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-amin ocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) on synaptic transmiss ion and excitability of phrenic motoneurons (PMNs) in an in vitro neon atal rat brainstem/spinal cord preparation. The effects of 1S,3R-ACPD were multiple, including reduction of inspiratory-modulated synaptic c urrents and increase of neuronal excitability via an inward current (I -acpd) associated with a decrease of membrane conductance. The mechani sm underlying synaptic depression was examined. We found that IS,3R-AC PD 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 b y presynaptic mGluRs. We also examined the ionic basis for I-acpd. We found that I-acpd had a reversal potential of approximately -100 mV, c lose to the estimated E(K+) (-95 mV). Elevating extracellular [K+] to 9 mM reduced the I-acpd reversal potential to -75 mV. The K+ channel b locker Ba2+ induced an inward current with a reversal potential at -93 mV associated with a decrease of membrane conductance, closely resemb ling the effect of 1S,3R-ACPD. Moreover, Ba2+ occluded 1S,3R-ACPD effe cts. In the presence of Ba2+, I-acpd and the 1S,3R-ACPD-induced decrea se of membrane conductance were diminished. Our data indicate that the dominant component of I-acpd results from the blockade of a Ba2+-sens itive resting K+ conductance. We conclude that the activation of mGluR s affects the inspiratory-modulated activity of PMNs via distinct mech anisms at pre- and postsynaptic sites.