Cellular and molecular mechanisms of nitric oxide-induced heart muscle relaxation.

1. The nitric oxide (NO) donor S-nitro-N-acetyl-penicillamine (SNAP) inhibits Helix aspersa heart activity and relaxes muscles. 2. K-free saline and ouabain both depress SNAP-induced relaxation in most experiments, but in a few preparations they either had no effect or potentiated SNAP-induced relaxation. 3. Na-K pump reactivation following preincubation in K-free saline leads to the pronounced transient relaxation of heart muscle, the magnitude of which depends on the duration of preincubation. 4. 0.1 mM SNAP inhibited the ouabain sensitive part of 86Rb uptake, which reflects Na-K pump activity. This inhibition is potentiated by phospholipase C. 5. SNAP increased cGMP levels in the heart. 6. These results indicate that SNAP-induced relaxation depends on Na and Ca gradients across the membrane, which suggests that Na:Ca exchange is involved in the mechanisms of SNAP-induced relaxation. It is postulated that SNAP elicits its inhibitory effect on the heart through a cGMP-dependent Na:Ca exchange.

Metabotropic GABA receptors regulate acetylcholine responses on snail neurons.

1. The A type of acetylcholine response of Helix neurons is downmodulated by low concentrations of GABA that do not elicit any measurable change in membrane potential or conductance. 2. We find that these physiological actions are associated with an increase in both intracellular cyclic AMP levels and 45Ca2+ influx. 3. The modulation of the acetylcholine response by GABA is blocked when the neurons are injected with EGTA to prevent a rise in intracellular Ca2+ concentration or when tolbutamide, an inhibitor of protein kinase A, is applied. 4. These results are consistent with the effects of GABA being mediated by a metabotropic GABA receptor that is activated at very low GABA concentrations and mediates modulation of the acetylcholine response via regulation of intracellular Ca2+ and cyclic AMP levels.

[The metabolic pathways of concanavalin A action on the chemosensitivity of the neuronal membrane]. / Metabolicheskie puti vozdeistviia konkanavalina A na khemochuvstvitel'nost' membrany neironov.

It has been shown that concanavaline A (Co A) inhibited those acetylcholine (ACh) and gamma-aminobutyric acid (GABA) responses of the membrane of dialyzed snail neurons which were blocked by ouabain. The inhibitory effect of Co A on these responses was removed at 5 degrees C. Co A had no significant influence on ACh responses which were insensitive to ouabain. Co A inhibited ACh-induced 86Rb+ ions efflux from the neurons preliminarily enriched by these ions. Co A has exerted a stimulating effect on the phosphorylation of neuronal membrane fractions. In this case Co A decreased the intracellular cyclic adenozine monophosphate (cAMP) content and increased the intracellular content of cyclic guanozine monophosphate. It is supposed that cAMP-independent membrane phosphorylation underlies the Co A inhibiting effect on the neuronal membrane sensitivity to ACh and GABA.

[The action of alpha-bungarotoxin on the acetylcholine responses of the membrane of snail neurons]. / Deistvie al'fa-bungarotoksina na atsetilkholinovye otvety membrany neironov ulitki.

The effect of alpha-bungarotoxin (alpha-BT) on two types of acetylcholine (ACh)-induced currents distinguished by their desensitization properties was studied on the isolated dialyzed Helix neurons by a concentration clamp method. It was shown that alpha-BT depressed both types of ACh responses and this action was reversible in the majority of experiments. The depressive action of alpha-BT on ACh-induced currents occurred only in the presence of albumin, though albumin itself had no effect on the ACh responses. The concentration dependence of the blocking effect of alpha-BT on ACh-induced currents in both types of neurons was studied. The calculated values of alpha-BT concentration which caused 50% depression of the ACh-induced current were (13.85 +/- 1.25) X 10(-8) and (5.56 +/- 1.0) X 10(-8) g/ml for A and B types of neurons, respectively.

[Effect of ionizing radiation on the functional state of snail neurons. Cyclic nucleotide levels and phosphorylation of membrane proteins]. / Deistvie ioniziruiushchei radiatsii na funktsional'noe sostoianie neironov vinogradnoi ulitki. Soderzhanie tsiklicheskikh nukleotidov i fosforilirovanie membrannykh belkov.

A study was made of the effect of ionizing radiation, phospholipase A2, and low concentrations of mediators (for instance, acetylcholine and gamma-aminobutyric acid) on the content of cyclic nucleotides and phosphorylation of membrane proteins of Helix pomatia nervous ganglia. Ionizing radiation was shown to decrease considerably the levels of cAMP and cGMP which correlated with the diminution of membrane phosphorylation. Phospholipase A2 and low doses of mediators produced a modifying effect on the cyclic nucleotide content.