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T G Smart

Publications and source records attributed to T G Smart.

78 records · Page 5Linked to original sources
PubMed1982

A novel effect of zinc on the lobster muscle GABA receptor.

The effect of zinc (and copper) was investigated on the lobster muscle gamma-aminobutyric acid (GABA) receptor. Zinc (10 microns-1 mM) depressed the GABA-evoked conductance increase in a fully reversible manner by possibly binding to an imidazole group, suggested from pH titration studies on the evoked-chloride conductance. Other transition metal (period 4) divalent cations (up to 500 microM) were inactive in antagonizing GABA responses. Variation of external chloride or anion substitution did not perturb the zinc antagonism; however, decreasing the pH markedly decreased the potency of zinc. A possible explanation for these results is discussed. Although the zinc antagonism resembled that produced by picrotoxinin, combination of these two agents depressed the GABA dose--conductance curve in a manner expected for two antagonists acting on independent sites. The zinc binding site was also discrete from the GABA recognition site; the results are interpreted in terms of a distinct binding site for zinc and H+. The distortion of an agonist dose--response curve by formation of an inactive agonist-divalent cation complex is discussed; however, complexation of GABA did not explain the observed antagonism by zinc. By comparison, zinc had no effect on the GABA responses of rat ganglionic neurons. It is concluded that the zinc binding site, on lobster muscle, may be an important modulatory site for the GABA-evoked chloride conductance.

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PubMed1982

Measurement of GABA-evoked conductance changes of lobster muscle fibres by a three-microelectrode voltage clamp technique.

The effective membrane conductance and capacity of lobster muscle fibres was measured by a three-intracellular-microelectrode voltage clamp technique. Conductance values agreed well with those determined under current clamp, by means of the 'short' cable equations. Reversible increases in conductance evoked by gamma-aminobutyric acid (GABA) were reflected by differences (delta V) in electrotonic potential amplitude recorded at the centre, and midway between the centre and fibre end respectively. GABA dose--conductance curves derived from cable theory or from delta V measurements were virtually identical. The effective capacity (ceff), determined from the area beneath the 'on' delta V capacity transient, yielded values of the membrane time constant consistently lower than those obtained by the graphical method of E. Stefani & A.B. Steinbach (J. Physiol., London. 203, 383-401 (1969)); one possible explanation for this discrepancy is discussed. In the presence of GABA, the effective capacity was reduced in a dose-related manner. The results were interpreted in terms of an equivalent circuit in which surface membrane was arranged in parallel with cleft-tubular membrane of finite conductance, charged through an access resistance. GABA was though to be decreasing ceff by selectively increasing the conductance of the cleft-tubular membranes.

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PubMed1981

A re-examination of the GABA-inhibitory action of bicuculline on lobster muscle.

The GABA-inhibitory action of bicuculline on lobster muscle was critically re-examined. Bicuculline (20-100 micrometers) depressed the GABA-evoked conductance increase in a reversible manner, the double reciprocal transformation of the GABA dose/conductance curves remaining linear. If bicuculline was assumed to be a pure non-competitive antagonist, then the observed depression of the GABA curves at high GABA concentrations was underestimated. Also, the action of bicuculline was not in accordance with a dualistic antagonism (competitive and pure non-competitive type). Regarding bicuculline as a "mixed" non-competitive antagonist however, gave a better overall fit to the experimental data. Combinations of bicuculline and picrotoxinin also depressed the GABA response in a manner expected from the combination of two "mixed" non-competitive antagonists. It was concluded that bicuculline (like picrotoxinin and picrotoxin) behaves as a "mixed" non-competitive rather than a pure non-competitive antagonist of GABA on lobster muscle. However bicuculline methochloride proved inactive on the lobster. Moreover, bicuculline itself became less effective in a more acidic solution (pH 5.6, where more of the protonated form would exist). An intracellular or intramembrane site of action of this antagonist was therefore postulated.

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PubMed1980

Do motor-nerve terminals have gamma-aminobutyric acid receptors?

1 gamma-Aminobutyric acid (GABA, 0.1 to 1 mM) had no significant effect on the amplitude, rise time, half decay time or frequency of miniature endplate potentials (m.e.p.ps) at the frog or mouse neuromuscular junctions in vitro. 2 Addition of GABA (1 mM) to preparations previously treated with 11 mM K+-Ringer did not cause any further increase in m.e.pp. frequency. GABA also failed to increase the m.e.p.p. frequency in a low Cl--Ringer. 3 GABA (0.1 to 1 mM) did not reduce the high m.e.p.p. frequency induced by veratrine (20 to 40 mg/l). 4 GABA (0.5 to 1 mM) did not affect the amplitude of the extracellularly-recorded nerve terminal spike, whereas 15 mM [K+] reduced the spike. 5 The quantal content (m) of the evoked endplate potential was not significantly altered by GABA; 9 mM [K+] significantly increased m. 6 When external d.c. potential differences were recorded in a three-chambered bath, GABA (0.1 to 1 mM) produced a very small depolarization if applied to the phrenic nerve trunk, but not if applied to the pre-terminal axon/motor nerve terminal region. Carbachol (0.3 to 1 mM) evoked a small depolarization when applied to the nerve terminal chamber. 7 These results fail to provide evidence for the existence of GABA receptors on motor nerve terminals.

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PubMedDate not supplied

Expression of functional GABA, glycine and glutamate receptors in Xenopus oocytes injected with rat brain mRNA.

The use of Gurdon's Xenopus oocyte translation system has allowed the production of neurotransmitter receptors in a foreign cell membrane, following the translation of microinjected mRNA isolated from various sources. This very accessible and relatively simple preparation permits the study of the requirements for receptor-ionophore function, assembly and membrane integration. This analysis is presently feasible for the peripheral nicotinic acetylcholine receptor, the chick brain gamma-aminobutyrate (GABA) receptor and the rat brain serotonin receptor. We now report the novel and successful expression of the GABA, glycine, glutamate and related acidic amino acid receptors of mammalian brain, and show that they exhibit pharmacologically separate identities when their mRNAs are processed in the amphibian oocyte.

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