Biphasic Action of Glutamic Acid and Synaptic Inhibition in an Identified Serotonin-containing Neurone

SUMMARY1. The membrane currents evoked by glutamate agonists on isolated and identified neurones of molluscan pedal ganglia were investigated using the voltage clamp technique.2. The fast chloride current (Er (reversal potential) =-41 mV) evoked in a Ped-9 neurone by application of glutamate, quisqualate and ibotenic acid could be blocked by furosemide (0-1 mM). The slow potassium current (Er = -85 mV) evoked in Ped-8 and Ped-9 neurones by glutamate, quisqualate and kainate could be blocked by tetraethylammonium (50 /M).3. N-Methyl-D-aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) failed to induce a response in neurones studies.4. The spider venoms argiopine and argiopinine III (50-500 nM) selectively inhibited quisqualate-induced potassium current, but had no influence on glutamate-, ibotenate-or quisqualate-induced chloride and kainate-induced potassium currents. Glutamate-induced potassium current was partially inhibited by argiopine and argiopinine III.5. The existence of several types of distinct glutamate receptors was confirmed in cross-desensitization experiments, and a lack of interaction was observed between quisqualate and kainate.6. Potassium currents induced both by quisqualate and kainate strongly depended on temperature and could be blocked by pertussis toxin. Intracellular injection of the calcium chelator, EGTA, did not affect quisqualate and kainate responses.7. In neurones loaded with non-hydrolysable GTP analogues, GTP-y-S (guanosine-5'-O-(3-thio)triphosphate) or GppNHp (5'-guanylylimidodiphosphate), the potassium current was gradually induced in the absence of agonists. As this current progressed, the magnitude of the glutamate-or kainate-evoked current transients became smaller and finally negligible. The GTP-y-S-induced current was not inhibited by argiopine.

Section: Ionic Basis Of Glu Responsementioning

confidence: 77%

Different types of glutamate receptors in isolated and identified neurones of the mollusc Planorbarius corneus.

Bolshakov

Gapon

1991

“…Usually, glutamate opens cation channels, which have a rather poor selectivity between sodium and potassium and typically have a reversal potential around 0 mV (Hablitz & Langmoen, 1982;Mayer & Westbrook, 1984). In addition, glutamate has been shown to open chloride channels in invertebrate neurones and muscle cells and in vertebrate cones (Szczepaniak & Cottrell, 1973;Cull-Candy, 1976; Sarantis, Everett & Attwell, 1988).…”

Section: Introductionmentioning

confidence: 99%

Electrogenic uptake of glutamate and aspartate into glial cells isolated from the salamander (Ambystoma) retina.

Barbour

Brew

Attwell

1991

186

166

SUMMARY1. The effects of excitatory amino acids on the membrane current of isolated retinal glial cells (Muller cells) were investigated using whole-cell patch clamping.2. L-Glutamate evoked an inward current at membrane potentials between -140 and +50 mV. The current was larger at more negative potentials.3. The glutamate-evoked current was activated by external cations with relative efficacies: Na+ > Li+> K+ > Cs+, choline. It was activated by internal cations with relative efficacies K+ > Rb+ > Cs+ > choline. Chloride and divalent cations did not affect the glutamate-evoked current.4. Raising the intracellular sodium or glutamate concentrations, or raising the extracellular potassium concentration, reduced the current evoked by external glutamate. The suppressive effect of internal glutamate was larger when the internal sodium concentration was high.5. Some analogues of glutamate also evoked an inward current. Responses to Laspartate resembled those to glutamate, but for aspartate the apparent affinity was higher and the voltage dependence of the current was steeper. In the physiological potential range the current evoked by a saturating dose of aspartate was less than that evoked by a saturating dose of glutamate.6. The uptake blocker threo-3-hydroxy-DL-aspartate (30,tM) reduced the glutamate-evoked current, but also generated a current itself. Dihydrokainate (510 /LM) weakly inhibited the glutamate-evoked current without generating a current itself.7. The commonly used blockers of glutamate-gated ion channels, 2-amino-5-phosphonovalerate (APV; 100 ,M), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 /bM), and kynurenate (1 mM) had no effect on the glutamate-evoked current. 8. The voltage dependence, cation dependence and pharmacological profile of the current evoked by excitatory amino acids indicate that it is caused by activation of the high-affinity glutamate uptake carrier. This carrier appears to transport one glutamate anion into the cell, one K+ ion out of the cell, and two or more Na+ ions into the cell, on each carrier cycle. At the inner membrane surface some or all of the transported Na+ dissociates from the carrier after the transported glutamate has dissociated.MS 8441

“…The question therefore arises as to whether glu can elicit direct hyperpolarizing responses as has been observed in the nervous system of certain invertebrates (cf. Szczepaniak & Cottrell, 1973) or whether the glu-a.h. is generated by some other mechanism, such as electrogenic Na+ pumping as originally considered by Zieglgaensberger & Puil (1973). In sympathetic ganglia, the depolarization induced by the nicotinic action of acetylcholine (ACh) is also followed by an afterhyperpolarization (ACh-a.h.) (Pascoe, 1956).…”

Section: Introductionmentioning

confidence: 99%

The role of the electrogenic sodium pump in the glutamate afterhyperpolarization of frog spinal cord.

Padjen¹,

Smith²

1983

SUMMARY1. Drug responses of isolated hemisected frog spinal cords were examined by means of the sucrose-gap technique. The glutamate-induced depolarizations (glu-d) of motoneurones (recorded from ventral roots), and primary afferents (recorded from dorsal roots), were followed by an afterhyperpolarization (glu-a.h.). The depolarization induced by DL-homocysteic acid (DLH) was only occasionally followed by an afterhyperpolarization (DLH-a.h.).2. The glu-a.h. on both roots persisted in the presence of tetrodotoxin (TTX, 0.1-1 /M), or Ringer solution containing 10 mM-Mg2+; 041 mM-Ca2+ or 2 mM-Mn2+; 0-2 mM-Ca2+. This indicated that the response was neither due to the release of endogenous neurally active substances nor to the activation of a Ca2+-sensitive K+ conductance.3. The glu-a.h. was reduced or blocked by K+-free Ringer solution, 3-acetylstrophanthin (3-Ac-Str; 1 /UM) or Li+ ions, and was therefore attributed to the activity of the electrogenic Na+ pump.4. The duration of depolarization induced by glu or DLH was increased in the presence of K+-free Ringer solution, 1 ,UM 3-Ac-Str or Li ions. It is therefore