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Biomedical subjects

A Gorio

Publications and source records attributed to A Gorio.

At least 109 records · Page 6Linked to original sources
PubMed1983

Muscle reinnervation--I. Restoration of transmitter release mechanisms.

Following sciatic nerve crush the restoration of neuromuscular transmission in the extensor digitorum longus muscle of rat proceeds in a well defined manner: (a) as soon as the nerve-muscle contact is reformed, a subthreshold end-plate potential is recorded; no 'non-transmitting stage' is observed; (b) 24 hours later muscle action potentials are induced by nerve stimulation; (c) miniature end-plate potentials are absent or very rare at the newly reinnervated end-plates; their frequency returns to normal in about 4 weeks; (d) the frequency is also very much reduced in 30 mM K+ and hypertonic solutions and recovers slowly, in 4 and 5 weeks, respectively, while black widow spider venom is from the beginning as powerful as in normal neuromuscular junctions; (e) at the early stages of reinnervation the Ca2+-dependent release mechanisms are much stronger than control cases, while the Ca2+-independent mechanisms are weaker and recover in 5 weeks. The gradual reassembly and restoration of neurotransmitter release mechanisms of the extensor digitorum longus nerve terminal indicate the complexity of pre-synaptic ending organization.

Animals↗
PubMed1983

Muscle reinnervation--II. Sprouting, synapse formation and repression.

Extensor digitorum longus muscle is reinnervated by the regenerating neurites at the end-plate region; as soon as the contact is made, the rate of neurite elongation inside the cleft decreases about 1000-fold while interfibre growth and sprout formation proceed unchanged. Polyinnervation reaches the maximum level 7-10 days after reinnervation, then synaptic repression begins. The elimination of redundant innervation takes place when the biophysical properties of the muscle are again normal. There is no sign of either phagocytosis or degeneration, therefore the process of synaptic repression is probably due to retraction, as neurites do when in culture. The role of Schwann cells and nerve sheath in the process of maintenance is suggested.

Animals↗
PubMed1983

Muscle reinnervation--III. Motoneuron sprouting capacity, enhancement by exogenous gangliosides.

Rat soleus muscle was partially denervated by resecting the L5 mixed nerve. Muscle reinnervation was monitored 10, 30 and 50 days after surgery. The extent of recovery was found to be dependent on the number of axons remaining in the muscle and appeared not to be influenced by the time allowed. If animals were treated daily with 5 mg/kg of gangliosides the enlargement of the motor units was further enforced. The index of sprouting (expressed as the ratio between the percentage of muscle reinnervation due to a certain number of motor neurons in reinnervation and in normal conditions) was increased in a significant way by gangliosides treatment, i.e. one motor unit can expand up to about 4.5-fold, but if the animal was treated with gangliosides the motor unit can expand up to about 6.3-fold. These results showed that motoneuron sprouting capacity is increased by treatment animals with gangliosides.

Animals↗
PubMed1979

Avermectin B1a irreversibly blocks postsynaptic potentials at the lobster neuromuscular junction by reducing muscle membrane resistance.

Avermectin B1a, a macrocyclic lactone with broad spectrum anthelmintic activity, affects neuromuscular transmission in the lobster stretcher muscle. Perfusion of the muscle with 1-10 microgram of the drug per ml eliminates inhibitory postsynaptic potentials within a few minutes. Intracellularly recorded excitatory postsynaptic potentials are gradually reduced in amplitude over 20-30 min, and their falling phases become faster; there is no effect, however, on extracellularly recorded excitatory potentials. Avermectin B1a reduced the input resistance of the muscle fibers with a time course similar to that of the reduction of excitatory potentials. Washing for up to 2 hr with drug-free solution fails to reverse the drug's effects. However, perfusion with 20 microgram of picrotoxin per ml results in recovery of the excitatory potentials and input resistance. Avermectin B1a also blocks the firing of the crayfish stretch receptor neuron, and this block is also reversed by picrotoxin. We hypothesize that the reduction in excitatory postsynaptic potentials after avermectin B1a treatment is caused solely by reduction in membrane resistance; additional experiments suggest that the reduction in membrane resistance is due to the opening of membrane Cl- channels, perhaps including those regulated by gamma-aminobutyric acid at the inhibitory synapse.

Animals↗
PubMed1979

Reversibility and mode of action of Black Widow spider venom on the vertebrate neuromuscular junction.

Black widow spider venom (BWSV) stimulates transmitter release and depletes synaptic vesicles from muscles bathed in a sodium free medium containing 1 mM EGTA. However, frog neuromuscular junctions treated with BWSV in glucosamine Ringer's and post-treated with antivenin recover normal function. This suggests that probably the permanent block of neuromuscular transmission is due to changes in permeability of the nerve ending plasma membrane to cations such as Na+. When BWSV is applied in a medium lacking divalent cations and containing 1 mM EGTA, in most of the cases no effect is observed. We found that this inhibition can be overcome in three ways: (a) by adding divalent cations to the medium; (b) by increasing the tonicity of the medium with sucrose; (c) by raising the temperature of the medium. These results suggest that the lack of divalent cations influences the membrane fluidity. Moreover, in view of the report by Yahara and Kakimoto-Sameshima (1977. Proc. Natl. Acad. Sci. U.S.A. 74:4511--4515) that hypertonic media induce capping of surface receptors in lymphocytes and thymocytes, we think that these data further support the hypothesis that BWSV stimulates release by a dual mode of action; namely, it increases the nerve ending permeability to cations and also stimulates release directly via a process of redistribution of membrane components, a process which may also inhibit vesicle recycling.

Animals↗
PubMed1978

Effect of concanavalin A on black widow spider venom activity at the neuromuscular junction: implications for mechanisms of venom action.

Concanavalin A (Con A) inhibits black widow spider venom-induced transmitter release at both tissue-cultured and adult neuromuscular junctions and also inhibits the venom-induced destruction of cultured neurites. This inhibitory action is partially or completely prevented by prior treatment with colchicine. Neither colchicine nor Con A interacts significantly with depolarization-induced transmitter release. These results are analogous to those obtained from experiments on lymphocyte surface receptor capping. They suggest that redistribution of neuronal membrane components may be a crucial step in spider venom action. This membrane redistribution appears to be modulated in neurons, as in other cell types, by microtubule-microfilament array. How such a redistribution causes increased transmitter release cannot as yet be specified. Changes in the ionic permeability of sodium and potassium were examined as likely mechanisms. Increased sodium influx (and seondary release of calcium from intracellular stores) cannot be the basis for spider venom action. Increased potassium efflux remains a possibility, but is not consistent with all of the data. Other possible mechanisms are also suggested.

Animals↗
PubMed1978

Double mode of action of black widow spider venom on frog neuromuscular junction.

Black widow spider venom (BWSV) contains a toxin, alpha-latrotoxin, which is capable of stimulating vesicle release, resulting eventually in depletion of vesicles and block of neuromuscular transmission at the frog neuromuscular junction. Since it has been shown that alpha-latrotoxin very markedly increases the cation conductance of artificial lipid bilayers, it was postulated that BWSV stimulates release by opening channels permeable to Ca2+ and, in the case of Ca2+-free Ringer's, to Na+ which would release Ca2+ from intracellular stores. To test this hypothesis we chose as a sodium substitute, glucosamine, which is impermeable to the venom-induced channels in the lipid bilayers and to the postsynaptic membrane of the frog neuromuscular junction. Electron microscopical analysis showed that up to 75 min perfusion in Na+ and Ca2+-free medium did not alter the ultrastructure of the nerve terminals. However when BWSV was applied in this medium a significant depletion was noticeable within 15 min and after 60 min the terminals were depleted of vesicles whereas the mitochondria were unchanged in number and structure. If BWSV is applied for 60 min in glucosamine Ringer's containing 1.8 mM Ca2+, most of the nerve terminals still have synaptic vesicles scattered in the cytoplasm or clustered around amorphous structures and the mitochondria are swollen. Application of large doses of BWSV in low Ca2+ Ringer's leads to damage of the mitochondria and to very pronounced swelling of the nerve endings, whereas this is not observed if the dose of venom is applied in Na+-free and Ca2+-free Ringer's. Electrophysiological recording showed that neuromuscular transmission is already blocked after 15 min treatment with BWSV in glucosamine-Ringer's. From these results we conclude that BWSV increases the conductance of the nerve terminal membrane to cations such as Na+ and Ca2+ and stimulates release by a mechanism which may not involve its ionophore property.

Animals↗
PubMed1978

Acetylcholine compartments in mouse diaphragm. Comparison of the effects of black widow spider venom, electrical stimulation, and high concentrations of potassium.

We have studied the effects of 25 mM potassium, electrical stimulation of the phrenic nerve, and crude black widow spider venom on the ultrastructure, electrophysiology, and acetylcholine (ACh) contents of mouse diaphragms. About 65% of the ACh in diaphragms is contained in a depletable store in the nerve terminals. The rest of the ACh is contained in a nondepletable store that may correspond to the store that remains in denervated muscles and includes, in addition, ACh in the intramuscular branches of the phrenic nerve. About 4% of the ACh released from the depletable store at rest is secreted as quanta and may come from the vesicles, while 96% is secreted in a nonquantized form and comes from an extravesicular pool. The size of the extravesicular pool is uncertain: it could be less than 10%, or as great as 50%, of the depletable store. K causes a highly (but perhaps not perfectly) selective increase in the rate of quantal secretion so that quanta account for about 50% of the total ACh released from K-treated diaphragms. K, or electrical stimulation of the phrenic nerve, depletes both the vesicular and extravesicular pools of ACh when hemicholinium no. 3 (HC-3) is present. However, most of the vesicles are retained under these conditions so that the diaphragms are able to increase slightly their rates of release of ACh when K is added. Venom depletes the terminals of their vesicles and abolishes the release of quanta of ACh. It depletes the vesicular pool of ACh (since it depletes the vesicles), but may only partially deplete the extravesicular pool (since it reduces resting release only 10--40%). The rate of release of ACh from the residual extravesicular pool does not increase when 25 mM K is added. Although we cannot exclude the possibility that stimulation may double the rate of release of ACh from the extravesicular pool, our results are compatible with the idea that the ACh released by stimulation comes mainly from the vesicles and that, when synthesis is inhibited by HC-3, ACh may be exchanged between the extravesicular pool and recycled vesicles.

Acetylcholine↗