Glycine, GABA and synaptic inhibition of reticulospinal neurones of lamprey

Abstract

1. Intracellular recordings were made from the cell bodies and axons of giant reticulospinal neurones (Müller cells) of the lamprey and the effects of a variety of putative neurotransmitters tested. Bath-applied acetylcholine, carbamylcholine, norepinephrine, dopamine, histamine and serotonin were without effect. Glycine and gamma-aminobutyric acid (GABA) hyperpolarized and reduced the input resistance of cell bodies but had no effect on the membrane conductance of axons. 2. The threshold dose of bath-applied GABA or glycine for a conductance change in somata was about 0.5 mM and the maximum effect was reached at about 10 mM. The maximum conductance change produced by glycine was always greater than that produced by GABA. 3. Replacement of the sodium in the bathing saline with lithium or choline prolonged the conductance change produced by ionophoretically applied glycine or GABA, suggesting the presence of sodium-dependent uptake systems for glycine and GABA. 4. The reversal potentials for responses to ionophoretically applied glycine and GABA average about --83 mV, the same as that for the inhibitory post-synaptic potential (i.p.s.p.) produced in Müller cells by stimulation of the ipsilateral vestibular nerve. 5. The i.p.s.p. and drug responses appeared to involve an increase in chloride conductance, since their reversal potentials were shifted appropriately by changes in either internal or external chloride. 6. Changes in extracellular potassium concentration also changed i.p.s.p. and drug reversal potentials. However, these effects could be attributed to secondary changes in internal chloride. 7. The receptors for GABA and glycine appeared to be different because of the absence of cross-desensitization and because, at doses below 20 microM, picrotoxin and bicuculline selectively blocked GABA responses while strychnine selectively blocked glycine responses. 8. At concentrations of 20 microM, strychnine eliminated the i.p.s.p. while picrotoxin and bicuculline had no effect. Further, the i.p.s.p. and glycine response of Müller cells located in the isthmic region of the midbrain had the same threshold sensitivity to strychnine. However, the glycine response of other Müller cells was more sensitive to strychnine than was the i.p.s.p. 9. We conclude that glycine is a better candidate for the inhibitory transmitter onto Müller cells than is GABA.