Search PubMed⌕ Search

Biomedical subjects

R Anwyl

Publications and source records attributed to R Anwyl.

105 records · Page 6Linked to original sources
PubMed1979

Action of colchicine and cytochalasin B on the acetylcholine receptor.

1. The effects of colchicine and cytochalasin B have been investigated on the extrajunctional acetylcholine (ACh) receptors of rat muscle. 2. Colchicine and cytochalasin B each decreased the amplitude and rise time of the iontophoretic ACh potential. When the dose of ACh was increased in the presence of these agents, ACh potentials were produced with a biphasic waveform consisting of a fast initial phase and a second slow phase. 3. It is proposed that colchicine and cytochalasin B are acting through a mechanism other than the breakdown of microtubules and microfilaments.

Acetylcholine↗
PubMed1979

Studies on the permeability of the glutamate receptor at the insect neuromuscular junction.

Voltage clamp studies of the post-synaptic membrane of the locust neuromuscular junction have shown that the transmitter substance and L-glutamate cause an approximately equal increase in permeability to sodium and potassium. The changes in reversal potential caused by altering external potassium, but not external sodium, were similar to those predicted by the Goldman equation. The ionic channels of the glutamate receptor had a high permeability to a variety of inorganic and organic cations, indicating relatively non-selective channels of size approximately 0.6 x 0.4 nm.

Animals↗
PubMed1977

Accelerated degradation of acetylcholine receptor from cultured rat myotubes with myasthenia gravis sera and globulins.

Altered geometry of the neuromuscular junction and a decreased number of acetylcholine receptors appear responsible for the defect of neuromuscular transmission in myasthenia gravis. We have used cultured rat myotubes as a model to study in vitro the potential role of myasthenic globulins in the pathological process. Acetylcholine receptor content was assayed by the extent of 125I-labeled alpha-bungarotoxin binding, and acetylcholine receptor function was assayed by the sensitivity to acetylcholine iontophoresis. The half-life of the acetylcholine receptor was 18.5 hr in the presence or absence of control sera. Myasthenic sera and globulins produced a gradual reduction in acetylcholine receptors, as assessed by biochemical and electrophysiological techniques. The half-life in the presence of myasthenic sera was 6 hr. The accelerated turnover was unaffected by puromycin but was slowed by lowered temperature (18-20 degrees), interference with energy metabolism (2,4-dinitrophenol), and interference with cytoskeletal structures (colchicine and cytochalasin B). We found no electrophysiological evidence to suggest globulin blockade of acetylcholine access to the acetylcholine receptor. Our observations suggest that circulating globulins in myasthenia gravis may contribute to the functional defects of neuromuscular transmission by accelerating the rate of internationalization and degradation of surface membrane acetylcholine receptors.

Acetylcholine↗
PubMed1977

Permeability of the post-synaptic membrane of an excitatory glutamate synapse to sodium and potassium.

1. The changes in permeability of the post-synaptic membrane at the insect skeletal neuromuscular junction caused by the excitatory transmitter and L-glutamate have been studied using the voltage clamp technique. 2. The reversal potential (ER) of the excitatory post-synaptic current and the glutamate current was +3 and +4 mV respectively. 3. ER of the synaptic current did not change when external K was altered between 0 and 20 mM, but did show a small positive shift in 40 mM external K. Reducing external Na to 1-10 mM changes ER by 12-18 mV. Reducing external Cl to to zero caused no change in ER. 4. It is proposed that the transmitter and L-glutamate cause an increase in permeability to Na and K, but not to Cl. 5. In normal saline, the ratio of the permeability increase to Na and K (delta PNa/delta PK) is 0.9. 6. The changes in ER caused by altering external K were similar to those predicted by the Goldman-Hodgkin-Katz equation, assuming delta PNa/delta PK stays constant. 7. The changes in ER caused by alterations of external Na are much less than those predicted by the Goldman equation. 8. No glutamate current could be recorded in Na- and Ca-free saline either at the resting potential or at depolarized or hyperpolarized membrane potentials. 9. It is proposed that the outward K current is dependent upon the inward Na current, and that the increase in K permeability is abolished in zero external Na.

Animals↗
PubMed1977

The effect of foreign cations, pH and pharmacological agents on the ionic permeability of an excitatory glutamate synapse.

1. Voltage clamp studies of the post-synaptic membrane of the insect neuromuscular junction have shown that normal amplitude glutamate currents could be recorded for a limited time when external Na was completely replaced by Ca, Li, ammonium, methylamine and guanidine. No change in the reversal potential of the glutamate current was observed when Na was replaced by these ions. It is suggested that the glutamate ionic channel has a similar permeability to Na and to these foreign cations, although the foreign ions cause a longer-term block of the permeability increase or receptor function. 2. Procaine, pentobarbitone, 2-4-6-triaminopyrimidine, high and low pH and low temperature reduced the synaptic ionic permeability but did not alter the ratio of the conductance increase of Na to K (delta g Na/delta gK). 4-Aminopyridine and TEA did not reduce the synaptic ionic permeability. 3. The 3. The properties of the synaptic ionic channels resemble the tight junction transepithelial ionic channels of the mammalian gall-bladder, but are very different from the Na and K non-synaptic channels of axons. It is suggested that Na and K normally pass through a single relatively large channel containing strong proton accepting acidic ligands which render the channel cation selective.

Animals↗
PubMedDate not supplied

Modulation of vertebrate neuronal calcium channels by transmitters.

A large number of neurotransmitters have now been shown to reduce the amplitude and slow the activation kinetics of whole cell HVA ICa in a great diversity of neurons. These transmitters include L-glutamate (AMPA/kainate, metabotropic and NMDA receptors), GABA (via GABAB receptors, NA (via alpha 2 receptors), 5-HT, NA (via alpha 2 receptors), DA and several peptides. Both whole-cell and single-channel studies have demonstrated that the N-channel is the most common channel type to be blocked by transmitters, although an inhibition of the L-type channel has also occasionally been reported. The suppression of the N-type Ca current was commonly shown to be voltage-dependent, with a relief at large positive voltages. Strong evidence has been put forward showing that the transmitter action is mediated by a G-protein, with GDP-beta-S blocking transmitter action, and GTP-gamma-S directly inhibiting the Ca channel. Moreover, pertussis toxin blocked the transmitter action in most neurons, and following such block, injection of the G-protein Go restored transmitter action. A direct link between the G-protein and the Ca channel has been widely theorized to mediate the action of transmitters on certain neurons. There is also some evidence that certain transmitters in specific neurons mediate calcium channel inhibition through a 2nd messenger, perhaps protein kinase C. Transmitters have also been found, although uncommonly, to inhibit HVA L-type and LVA T-type channels. In addition, an enhancement of both HVA and LVA Ca currents by transmitters has been demonstrated, and substantial evidence exists for mediation of this action by cAMP.

Animals↗
PubMedDate not supplied

7-Nitro indazole, a selective neuronal nitric oxide synthase inhibitor in vivo, impairs spatial learning in the rat.

Nitric oxide (NO) is an intercellular messenger that has been suggested to have a role in learning and memory formation. Previous studies with nonselective NO synthase inhibitors have produced contradictory results in learning experiments. However, these drugs also produced blood pressure changes, as NO is an endothelial-derived relaxing factor. A novel NO synthase inhibitor, 7-nitro indazole (7-NI), as a dose (30 mg/kg i.p.) shown previously to inhibit neuronal NO synthase by 85% without affecting blood pressure, produced amnesic effects both in a water maze and in an 8-arm radial maze. Latency as well as distance was greater in the 7-NI group in the water maze while swim speed was not affected. Latency, working memory (WM), and reference memory (RF) errors were also higher in the 7-NI group in the 8-arm maze. At the end of the second training day, these differences were no longer apparent. However, on the fourth training day, a transfer test in the water maze showed that 7-NI had produced a spatial memory deficit, reducing quadrant bias and the number of annulus crossings. Learning of a visual cue task was not affected. No difference between groups was visible in an open field test. We conclude that neuronal NO synthase activity plays a role in learning and memory formation in the rat.

Animals↗