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D A Saint

Publications and source records attributed to D A Saint.

44 records · Page 3Linked to original sources
PubMed1987

Multiple actions of cadmium on transmitter release at the mouse neuromuscular junction.

The action of cadmium ions on transmitter release was studied at the neuromuscular junction in mouse diaphragm. In the presence of raised K+, Cd2+ caused a parallel shift to the right of the graph of transmitter release rate (frequency of miniature end-plate potentials, fmepp) versus log [Ca2+], with no change in maximum or slope, indicating a competitive mode of action of Cd2+. The apparent dissociation constant for Cd2+ was 3 microM. In calcium-free solutions containing 15 mM K+, Cd2+ caused a rise in the fmepp, which subsequently slowly declined despite the continued presence of Cd2+. The rise in fmepp caused by Cd2+ could be interrupted, but not reversed, by washing out the Cd2+ with EDTA. Exposure of the preparation to 100 microM Cd2+ for 15 min or more resulted in a raised fmepp that persisted despite the removal of Cd2+ and exposure to 200 microM EDTA. Following such treatment, the graph of fmepp versus log [Ca2+] continued to be shifted to the right. The interaction of Ca2+ with the residual effect of Cd2+ indicates that Cd2+, in addition to its action to block Ca2+ entry into the terminal, may act as a competitor and perhaps as a partial agonist at intracellular sites that normally bind Ca2+ and govern transmitter release. If this is the case, then it must be supposed that, in raised K+, quantal release of transmitter represents intermittent intense activation of release sites with local high levels of Ca2+ rather than continuous low level activation.

Algorithms↗
PubMed1986

Modification of motor nerve terminal excitability by alkanols and volatile anaesthetics.

A method of local polarization-excitation was used to study changes in motor nerve terminal excitability produced by n-alkanols and volatile anaesthetics in mouse diaphragm preparations. Ethanol and propanol caused an exaggeration of 'accommodation', i.e., the increase in excitation threshold produced by a conditioning depolarization. Butanol, hexanol and octanol had mixed effects, producing a rise in the minimum threshold (threshold after removal of resting accommodation) in addition to an increase in accommodation. Volatile anaesthetics produced effects on excitability at concentrations comparable to minimum alveolar concentration. The action of enflurane was essentially only to increase accommodation while methoxyflurane produced an increase in threshold insensitive to conditioning polarization. Halothane and isoflurane produced intermediate effects. Accommodation curves were little affected by Ba2+ or 4-aminopyridine and were consistent with accommodation being a reflection of inactivation of the Na+ current system. We conclude that volatile anaesthetics, at concentrations comparable to those producing anaesthesia, may substantially modify Na+ channel gating and inactivation.

1-Butanol↗
PubMed1986

Lanthanum as a surrogate for calcium in transmitter release at mouse motor nerve terminals.

The mechanism by which lanthanum (La3+) causes an increased frequency of miniature end-plate potentials (m.e.p.p.s) was studied at the mouse neuromuscular junction. At concentrations as low as 0.25 microM, La3+ caused a progressive rise in m.e.p.p. frequency, to a maximum of several hundred per second. 'Washing' with solution containing EDTA arrested the rise, but did not substantially reduce the raised m.e.p.p. frequency. At partially 'lanthanized' junctions high frequencies of m.e.p.p.s were maintained indefinitely, even in 0 Ca2+/EDTA solutions. The rate of development of high m.e.p.p. frequency was increased by repetitive nerve stimulation or by depolarization of the nerve terminal (high K+ or focally applied current), and appeared to be proportional to the concentration of La3+ over the range of 0.25-5 microM. At low concentrations of La3+ the rise of m.e.p.p. frequency depended upon the co-presence of a small amount of Ca2+ (greater than 10 microM) and was slowed and partially blocked by Cd2+, or by Ca2+ at about 10 microM. The quantal content of end-plate potentials was usually reduced in the presence of La3+, but was increased over control values after removal of La3+ by 'washing' with solution containing EDTA, once a raised m.e.p.p. frequency had developed. At partially lanthanized junctions the absolute increases in m.e.p.p. frequency produced by Ca2+ (in raised K+), ethanol, or by nerve stimulation in the presence of Ba2+, were greater than at control junctions, but in each case the increases in the logarithm of m.e.p.p. frequency were less than at control junctions. It is concluded that La3+ causes transmitter release only after entry into the nerve terminal via voltage-sensitive channels, probably those that normally admit Ca2+, that La3+ and Ca2+ may co-operate at internal sites to induce transmitter release, and that these ions both co-operate and compete at external sites that regulate their entry into the nerve terminal.

Action Potentials↗
PubMed1986

Effect of a volatile anesthetic upon presynaptic excitability in mammalian hippocampus.

Changes in presynaptic terminal axon excitability produced by enflurane in the rat hippocampal slice preparation were investigated by stimulation of Schaeffer collateral terminal axons and by recording single unit antidromic action potentials. Stimulating pulses were preceded by conditioning hyperpolarizing or depolarizing current pulses. A plot of net threshold for action potential generation against the conditioning pulse yields an "accommodation curve;" changes in this curve can be used to assess the mechanism by which changes in excitability are produced. Enflurane, at a concentration equivalent to approximately equal to 1.3 times the minimum alveolar concentration, reduced excitability of terminal axons and increased accommodation in a manner consistent with a possible change in the inactivation of gNa.

Action Potentials↗
PubMed1986

The actions of dimethyl sulfoxide on neuromuscular transmission.

The effects of dimethyl sulfoxide (DMSO) on subsynaptic response and quantal release of transmitter have been studied at the mammalian neuromuscular junction. Subsynaptically, at low concentrations (up to 1% by volume), DMSO prolongs the time course of decay of miniature endplate currents, (MEPCs), with no significant effect on the amplitude of the currents, which is consistent with an action of DMSO to inhibit acetylcholinesterase. At higher concentrations of DMSO (in excess of 1% by volume) the amplitude of MEPCs and the steady state response to carbamoylcholine (carbachol) are significantly reduced, which suggests an additional action of DMSO other than pure anticholinesterase activity. After pretreatment of the preparation with a low concentration of paraoxon, higher concentrations of DMSO decrease MEPC height and cause highly variable changes in the decay time course of the MEPC. The results suggest that DMSO concentrations in excess of 1% by volume have two distinct and opposite actions on the subsynaptic response; a pure anticholinesterase activity to enhance the response and a depressant effect which is similar to that caused by d-tubocurarine. Presynaptically, DMSO increased both the spontaneous release (measured as the frequency of miniature endplate potentials, fMEPP) and the evoked release (measured as the quantal content of endplate potentials). Both types of release were increased as an exponential function, with the same slope, of the DMSO concentration, suggesting a common mode of action on these two types of release. This action appeared not to be due to an effect on the disposition or effectiveness of calcium ions inside the terminal but, rather, was due to a fusogenic or global effect. In addition, the increase in fMEPP with DMSO was the same when external calcium was replaced by barium. At the concentrations studied, up to 8% by volume, DMSO did not cause any substantial depolarization of the nerve terminal or any appreciable change in the nerve terminal action potential. In a few experiments facilitation was studied at the frog neuromuscular junction and was unchanged by DMSO at concentrations which considerably enhanced transmitter release.

Acetylcholinesterase↗
PubMed1984

Cyclic nucleotide changes and contractility in the rat anococcygeus muscle.

The rat anococcygeus muscle can be activated by three different agonists, NA, ACh and KCl, each of these displaying a different degree of pharmacomechanical coupling. Investigation of cyclic nucleotide changes in the muscles when activated showed that changes in cAMP/cGMP ratio parallel changes in contractility. However, the cyclic nucleotide changes seem incidental to the process of contraction, rather than causally related to it.

Acetylcholine↗
PubMedDate not supplied

Effects of dietary n-3 fatty acids on contractility, Na+ and K+ currents in a rat cardiomyocyte model of arrhythmia.

The n-3 polyunsaturated fatty acids (PUFAs) have been reported to prevent ventricular fibrillation in human clinical studies and in studies involving experimental animals and isolated cardiomyocytes. This study aimed to determine whether dietary n-3 PUFAs could prevent isoproterenol and free radical-induced arrhythmic (asynchronous) contractile activity in adult rat cardiomyocytes and whether whole-cell Na(+) and K(+) currents measured by patch-clamp techniques were affected. Dietary supplementation with fish oil for 3 weeks significantly increased the proportion of total n-3 PUFAs in ventricular membrane phospholipids compared with saturated fat supplementation (18.8 +/- 0.6% vs. 8.1 +/- 1.0%, respectively). Cardiomyocytes from the fish oil group were less susceptible to isoproterenol-induced asynchronous contractile activity than were those from the saturated fat group [EC(50) values: 892 +/- 130 nM, n = 6 and 347 +/- 91 nM, n = 6 (P < 0.05), respectively]. Fish oil supplementation also prolonged the time taken to develop asynchronous contractile activity induced by superoxide and hydrogen peroxide. The voltage dependence of inactivation of Na(+) currents were significantly altered (-73.5 +/- 1.2 mV, n = 5 vs. -76.7 +/- 0.7 mV, n = 5, P < 0.05, for saturated fat and fish oil treated groups, respectively). The voltage dependence of activation of Na(+) and K(+) currents was not significantly affected by the dietary fish oil treatment. These results demonstrate the antiarrhythmic effects of dietary fish oil in a cardiomyocyte model of arrhythmia.

Journal Article↗