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gamma-Hydroxybutyrate (GHB) and GABA caused a hyperpolarization of cultured spinal, brainstem and cerebellar neurones. When KCl electrodes were used, the hyperpolarizations were reversed to depolarizations, suggesting that the actions of GHB and GABA are associated with an increase in conductance for chloride ions. Both the hyperpolarizations and depolarizations by these compounds were accompanied by an increase in membrane conductance and were reversibly blocked by the GABA antagonist bicuculline. It is suggested that GHB might either exert its effects by mimicking the action of GABA, or act as neurotransmitter or neuromodulator in the mammalian CNS.

The action of alpha- and beta-adrenoceptor agonists and antagonists has been studied on the membrane potential of glial cells in cultured rat central nervous system. Noradrenaline and the alpha-agonist phenylephrine caused a depolarization which was reversibly blocked by the alpha-antagonist phentolamine. In contrast, the beta-agonist isoprenaline hyperpolarized the glial membrane. This hyperpolarization was not associated with measurable changes in membrane resistance and was antagonized by the beta-blocker atenolol. These results suggest that the glial depolarization is mediated by activation of alpha-receptors, whereas the hyperpolarization is due to stimulation of beta-receptors. The existence of alpha- and beta-adrenoceptors on glial cells is further supported by autoradiographic studies showing binding of noradrenaline and alpha- and beta-antagonists to astrocytes.

The actions of dopamine, apomorphine and serotonin on the membrane potential of cultured astrocytes from rat spinal cord and striatum were examined. All three compounds caused a hyperpolarization of the majority of astrocytes tested. A small number of cells was depolarized and on a relatively large number of cells the amines had no effect. The dopamine antagonists cis-flupenthixol and domperidone reversibly blocked the effects of dopamine whereas the action of serotonin was antagonized by ketanserin. It is therefore concluded that the effect of both amines are due to activation of specific dopamine and serotonin receptors, respectively. Our electrophysiological data together with autoradiographic binding studies provide evidence that astrocytes possess receptors for dopamine and serotonin in addition to adrenoceptors and histamine receptors.

The action of glutamate and aspartate was studied on the membrane potential of human and rat spinal neurones in tissue culture. Both amino acids caused a depolarization of the cell membrane, the size of which was dependent on the concentration of the amino acids in the bathing fluid. In order to study ionic mechanisms associated with the amino acid depolarization, the ionic composition of the extracellular fluid was altered. Removal of sodium ions from the bathing solution reversibly reduced or abolished the depolarization produced by glutamate and aspartate suggesting that the action of these amino acids is associated with an increased sodium permeability. Substituting lithium for sodium ions also reversibly abolished the depolarization by glutamate indicating that in contrast to the effect of lithium on the action potential, this ion cannot replace sodium for the glutamate depolarization. These experiments show that the method of tissue culture is a suitable model to study ionic mechanisms underlying the action of neurotransmitters in the mammalian and especially in the human CNS.