Excitation of sympathetic preganglionic neurons via metabotropic excitatory amino acid receptors.

Abstract

The role of excitatory amino acid metabotropic receptors in the regulation of excitability of sympathetic preganglionic neurons was investigated. This study used both conventional intracellular and whole-cell patch clamp techniques to record from sympathetic preganglionic neurons in transverse spinal cord slices of the rat (9-21 days old). The metabotropic receptor agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) (10-200 microM, superfused for 2-60 s) and quisqualate (1-50 microM, superfused for 2-60 s) induced concentration-dependent depolarizing responses which did not desensitize. These responses were unaffected by the glutamate ionotropic receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10-50 microM), 6,7-dinitroquinoxaline-2,3-dione (DNQX, 10 microM), dizocilpine (MK-801, 10-40 microM), 3-[(R)-2-carboxy-piperazin-4-yl]-propyl-1-phosphonic acid (D-CPP, 10-50 microM) and DL-2-amino-5-phosphonovaleric acid (DL-AP5, 20-100 microM). Depolarizing responses to 1S,3R-ACPD and quisqualate were unaffected by L-2-amino-3-phosphonopropionic acid (L-AP3, 30 microM-1mM) and L-2-amino-4-phosphonobutanoic acid (L-AP4, 100 microM-1 mM)). The responses to 1S,3R-ACPD and quisqualate were reduced by including the G-protein blocker GDP-beta-S (400 microM) in the patch pipette solution by 77 +/- 2% (mean +/- S.E) of control (n = 3), suggesting that these agonists activate a G-protein-coupled receptor. Metabotropic receptor-mediated responses were maintained in the presence of tetrodotoxin (500 nM), progressively reduced with increased membrane hyperpolarization to around -95 mV and associated with either an increase of 16.5 +/- 2.8% (data from four neurons) in the majority of neurons (n = 22 of 34) or no measurable change (n = 12) in neuronal input resistance. These data suggest that the agonists exert a direct action on 1S,3R-ACPD and quisqualate had several effects on sympathetic preganglionic neuron membrane properties including: inhibition of a slow apamin-insensitive component of the afterhyperpolarization; a reduction in spike frequency adaptation leading to increases in firing frequency from 6.4 +/- 2.8 Hz in control experiments up to 14.7 +/- 3.0 Hz (n = 6 neurons) in the presence of a metabotropic receptor agonist: a broadening of the action potential by 37.5 +/- 6.4% (n = 6 neurons) of control. These observations suggest that the metabotropic receptor-mediated depolarization is due, at least in part, to the reduction of potassium conductances involved in the spike afterhyperpolarisation potential.(ABSTRACT TRUNCATED AT 400 WORDS)