Location of a delta-subunit region determining ion transport through the acetylcholine receptor channel

The combination of complementary DNA expression and single-channel current analysis provides a powerful tool for studying the structure-function relationship of the nicotinic acetylcholine receptor (AChR) (refs 1-5). We have previously shown that AChR channels consisting of subunits from different species, expressed in the surface membrane of Xenopus oocytes, can be used to relate functional properties to individual subunits. Here we report that, in extracellular solution of low divalent cation concentration, the bovine AChR channel has a smaller conductance than the Torpedo AChR channel. Replacement of the delta-subunit of the Torpedo AChR by the bovine delta-subunit makes the channel conductance similar to that of the bovine AChR channel. To locate the region in the delta-subunit responsible for this difference, we have constructed chimaeric delta-subunit cDNAs with different combinations of the Torpedo and bovine counterparts. The conductances of AChR channels containing chimaeric delta-subunits suggest that a region comprising the putative transmembrane segment M2 and the adjacent bend portion between segments M2 and M3 is involved in determining the rate of ion transport through the open channel.     

Hyperpolarization following activation of K+ channels by excitatory postsynaptic potentials

We have postulated that an excitatory postsynaptic potential (e.p.s.p.) may open voltage-sensitive K+ ('M') channels, in an appropriate depolarizing range, and that this could alter the e.p.s.p. waveform. Consequently, the fast e.p.s.p. in neurones of sympathetic ganglia, elicited by a nicotinic action of acetylcholine (ACh), could be followed by a hyperpolarization, produced by the opening of M channels during the depolarizing e.p.s.p. and their subsequent slow closure (time constant-150 mg). This introduces the concept that transmitter-induced p.s.ps may trigger voltage-sensitive conductances other than those initiating action potentials, and that in the present case this could produce a true post-e.p.s.p. hyperpolarization. (Some hyperpolarizations other than inhibitory postsynaptic potentials (i.p.s.ps) have been reported to follow e.p.s.ps.) We show here that this is so.     

Immunological selection of tumour cells which have lost SV40 antigen expression.

In an already tumorigenic spontaneously transformed mouse cell, after further transformation by SV40, the virus-specific antigenic function becomes dominant. By transplantation into syngeneic mice SV40 antigen negative revertant tumour cells can be selected out.     

Functional and molecular organisation of an antigen-specific suppressor factor from a T-cell hybridoma

Thymus-dependent (T) lymphocytes have been shown to have antigen specificity. The antigen receptor on T lymphocytes, in contrast to that on B lymphocytes, does not appear to be of the conventional immunoglobulin (Ig) type. Studies on the antigen-specific factors derived from helper and suppressor T cells (Ts) demonstrated that they possess determinants with antigen binding affinity and products of genes in the H-2 complex (MHC). Furthermore, antibodies against the variable region of Ig heavy chains or idiotypes have been shown to react with T-cell antigen receptors as well as antigen-specific helper and suppressor T-cell factors (TsF). It is, therefore, conceivable that at least two gene products are involved in the structural entity of these receptors: one each coded for by genes in either. To establish the molecular nature of the recognition component of T cells we have used homogeneous TsF from a T-cell hybridoma with a specific function. We report here that the antigen binding and I-J coded molecules on TsF are independently synthesised in the cytoplasm, and are secreted as an associated form of the two molecules; this association is required for antigen-specific suppression of antibody response.     

Effects of hypothalamic injections of 5,6-dihydroxytryptamine on thermoregulation in rats

Summary 5,6-Dihydroxytryptamine, a serotonin depletor, infused directly into the anterior hypothalamus of rat's brain, produced an increase in both heat production and heat loss (as indicated by changes in peripheral circulation) at temperatures of 8, 15 and 22°C. The rectal temperature of these treated rats remained constant.This work was supported by grants from National Science Council of Taiwan and J. Aron Charitable Foundation (USA). The author is grateful to Dr C. Y. Chai and Mr C. C. Wei for their support.     

The effect of two new peptide antibiotics,the hypelcins,on mitochondrial function

Summary The action on mitochondria of 3 peptide antibiotics, hypelcin-A, hypelcin-B, and alamethicin, was examined. The results showed that they are unique uncouplers of oxidative phosphorylation, with the same mechanism of action.     

Lack of correlation between structural features and function of synthetic agents tested for leukocyte chemotaxis

Summary A number of proteins, poly-L-amino acids, oligopeptides and lipids were tested for neutrophil, cosinophil and macrophage chemotactic activity. One myoglobin preparation was active. Based on the negative findings for all other substances, primary structure, secondary structure, degree of hydrophobicity, size and charge of a molecule, could be ruled out as structural features recognized by chemotactically responding phagocytes.I thank Dr J. H. Wissler for suggesting the reported experiments and Dr M. Landy and Prof. E. Sorkin for advice and criticism during preparation of this article. The excellent assistance by Mrs J. Kerschbaumer-Bech and Miss Margrit Bühlmann is gratefully acknowledged. This work was supported by Swiss National Foundation for Scientific Research, grant 3.8750.72, and by Sandoz-Stiftung, Basel.