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S R Barry

Publications and source records attributed to S R Barry.

17 recordsLinked to original sources
PubMed2000

Effects of adaptation of vestibulo-ocular reflex function on manual target localization.

The goal of the present study was to determine if adaptive modulation of vestibulo-ocular reflex (VOR) function is associated with commensurate alterations in manual target localization. To measure the effects of adapted VOR on manual responses we developed the Vestibular-Contingent Pointing Test (VCP). In the VCP test, subjects pointed to a remembered target following passive whole body rotation in the dark. In the first experiment, subjects performed VCP before and after wearing 0.5X minifying lenses that adaptively attenuate horizontal VOR gain. Results showed that adaptive reduction in horizontal VOR gain was accompanied by a commensurate change in VCP performance. In the second experiment, bilaterally labyrinthine deficient (LD) subjects were tested to confirm that vestibular cues were central to the spatial coding of both eye and hand movements during VCP. LD subjects performed significantly worse than normal subjects. These results demonstrate that adaptive change in VOR can lead to alterations in manual target localization.

Adaptation, Physiological↗
PubMed1997

The effect of visual context on manual localization of remembered targets.

This paper examines the contribution of egocentric cues and visual context to manual localization of remembered targets. Subjects pointed in the dark to the remembered position of a target previously viewed without or within a structured visual scene. Without a remembered visual context, subjects pointed to within 2 degrees of the target. The presence of a visual context with cues of straight ahead enhanced pointing performance to the remembered location of central but not off-center targets. Thus, visual context provides strong visual cues of target position and the relationship of body position to target location. Without a visual context, egocentric cues provide sufficient input for accurate pointing to remembered targets.

Adult↗
PubMed1997

Toxic effects of antimalarial drugs in Paramecium: role of calcium channels.

The antimalarial drugs, quinacrine, quinine and mefloquine, as well as the structurally-similar compound, W-7, inhibit calcium-dependent backward swimming and calcium currents in Paramecium calkinsi. These drugs are also toxic to paramecia at high concentrations. Therefore, one site of toxic action of the drugs may be the calcium channel. To test this hypothesis, the toxicity of the antimalarials and W-7 was compared in paramecia with and without calcium channels. Since calcium channels are located on the cilia, calcium channels were removed from the paramecia by deciliating the cells. Deciliated cells were found to be less susceptible to the lethal effects of the antimalarials and W-7 than their ciliated counterparts. Moreover, Pawns, mutants of P. tetraurelia that possess cilia but lack functional calcium channels, were also less susceptible to the antimalarials than wild-type cells. Thus, calcium channels may be one site of toxic action of the antimalarial drugs in paramecia and perhaps in other protists.

Animals↗
PubMed1994

Aminophylline enhances resting Ca2+ concentrations and twitch tension by adenosine receptor blockade in Rana pipiens.

1. We hypothesized that the xanthine aminophylline acts to block adenosine receptors on the surface of skeletal muscle fibres, thereby inhibiting a depressant action of endogenous adenosine. We further hypothesized that this action results in increased concentrations of intracellular resting Ca2+ and enhanced twitch tension upon muscle stimulation. 2. Peak twitch tension (Pt) of the semitendinosus muscle in normal frog Ringer solution (NFR) ranged from 6.8 to 9.4 g. Intracellular Ca2+ concentrations in control resting fibres ranged from 67 to 70 nM. Aminophylline at 100 microM produced increases of 26 and 22% in Pt and Ca2+ concentrations, respectively. 3. The adenosine receptor antagonists 8-phenyltheophylline (8-PT) and 1,3-dipropyl-7-methylxanthine (1,3-d-7-M) both increased Pt by 32% over values in NFR. In addition, 1,3-d-7-M increased resting Ca2+ concentrations by 29% over control levels. 4. Adenosine deaminase increased twitch tension and resting intracellular Ca2+ concentrations by 22 and 26% over controls, respectively. 5. N6-(2-phenylisopropyl)adenosine (R-PIA, 1 microM), a potent adenosine analogue, partially blocked both the increase in Pt and intracellular Ca2+ concentrations induced by the xanthines, possibly by competing for the adenosine receptor. 6. The data herein provide support for the existence of adenosine receptors on the membranes of skeletal muscle fibres and suggest a possible role for adenosine receptors in the regulation of twitch tension.

Adenosine↗
PubMed1993

Antimalarial drugs inhibit calcium-dependent backward swimming and calcium currents in Paramecium calkinsi.

The antimalarial drugs, quinacrine, chloroquine, quinine, primaquine, and mefloquine, share structural similarities with W-7, a compound that inhibits calcium-dependent backward swimming and calcium currents in Paramecium. Therefore, we tested whether antimalarial drugs also inhibit backward swimming and calcium currents in P. calkinsi. When the Paramecium is depolarized in high potassium medium, voltage-dependent calcium channels in the ciliary membrane open causing the cell to swim backward for 30 to 70 s. Application of calcium channel inhibitors, such as W-7, reduce the duration of backward swimming. In 0.05 mM calcium, quinacrine, mefloquine, quinine, chloroquine, primaquine and W-7 all reduced the duration of backward swimming. These effects were seen in sodium-containing and sodium-free high potassium solutions as well as sodium-free depolarizing solutions containing potassium channel blockers. In these low calcium solutions, backward swimming was inhibited by 50% at concentrations ranging from 100 nM to 30 microM. At higher calcium concentrations (1 mM or 15 mM), the effects of the antimalarials and W-7 were reduced. The effects of quinacrine and W-7 were tested directly on calcium currents using the two microelectrode voltage clamp technique. In 15 mM calcium, 100 microM quinacrine and 100 microM W-7 reduced the peak calcium current by 51% and 42%, respectively. Thus, antimalarial drugs reduce calcium currents in Paramecium calkinsi.

Animals↗
PubMed1992

Aminophylline increases submaximum power but not intrinsic velocity of shortening of frog muscle.

We hypothesized that methylxanthines, such as aminophylline, increase the power developed by submaximally activated frog skeletal muscles by increasing the force developed at any given velocity of shortening. Frog semitendinosus muscles were excised and tested at 20 degrees C in oxygenated control and aminophylline Ringer solutions. Force-velocity relationships were determined and power was calculated from muscles stimulated at frequencies of 80 and 300 Hz. The 300-Hz frequency of stimulation produced a maximum rate of force development. In 50 and 500 microM aminophylline, twitch force increased by 25 +/- 12 and 75 +/- 13%, respectively. Aminophylline did not affect maximum isometric force generation or the shortening velocity at any relative load. At 80-Hz stimulation and in the presence of 500 microM aminophylline, power increased by an average of 11% at 10 of 14 relative loads. At maximum frequencies of stimulation, aminophylline had no effect on any measured parameter. We conclude that aminophylline increases the power developed by submaximally activated frog muscles through an increase in the force generated particularly at the lower velocities of shortening.

Aminophylline↗
PubMed1991

Clinical implications of basic neuroscience research. I: Protein kinases, ionic channels, and genes.

Clinical implications of three areas of basic neuroscience research are described in this review paper. These areas include: (1) the discovery of protein kinase C and its implications for diabetic neuropathy, (2) analysis of single ionic channels and the basis of Lambert-Eaton myasthenic syndrome and cystic fibrosis, and (3) the cloning of genes for Duchenne muscular dystrophy and cystic fibrosis and new approaches to the treatment of these diseases.

Animals↗
PubMed1990

Adenosine depresses spontaneous transmitter release from frog motor nerve terminals by acting at an A1-like receptor.

Adenosine (1 microM to 1 mM) depressed spontaneous transmitter release from frog motor nerve terminals without producing any observable postsynaptic effects. Since this action of adenosine was blocked by 20 microM theophylline and 1 microM 8-phenyltheophylline, adenosine probably acts at a specific receptor on motor nerve terminals to reduce spontaneous transmitter output. The effects of the adenosine analogs, L-N6-phenylisopropyladenosine (L-PIA, 100 pM to 1 microM), D-PIA (100 nM to 100 microM), and 5'-N-ethylcarboxamidoadenosine (NECA, 10nM to 100 microM), were tested on spontaneous transmitter release at the frog neuromuscular junction. L-PIA depressed mepp frequency at a threshold concentration of about 1 nM, was thirteen times more potent than NECA, and was 294 times more effective than D-PIA. The rank-order potency of these analogs indicates that adenosine acts at an A1-like receptor to depress spontaneous transmitter release. Inhibitory actions of maximally effective concentrations of adenosine and L-PIA were also blocked by the A1-specific antagonist, 1-3-dipropyl-8-cyclopentylxanthine (DPCPX) at a concentration of 100 nM. Micromolar concentrations of NECA, an agonist with approximately equal affinity for the A1 and A2 receptors, produced biphasic effects on mepp frequency. Thus, a second adenosine receptor, perhaps of the A2 subtype, may be present on motor nerve terminals and may mediate an increase in spontaneous transmitter release.

Acetylcholine↗
PubMed1989

Aminophylline enhances contractility of frog skeletal muscle: an effect dependent on extracellular calcium.

The effects of aminophylline (10-500 microM) on isometric twitch and tetanic forces were studied in vitro on frog semitendinosus muscle. Two hypotheses were tested: 1) that micromolar concentrations of aminophylline enhanced contractility of isolated skeletal muscle and 2) that the potentiating effect of aminophylline was dependent on the presence of extracellular calcium ions. Muscles were removed, placed in aerated Ringer solution at 20 degrees C, attached to a force transducer, and stimulated directly. Muscles in normal Ringer and aminophylline Ringer were compared throughout the frequency-force relationship from twitches to maximum tetanic force. Aminophylline increased twitch force significantly at concentrations as low as 25 microM. Over a range of stimulation frequencies, but especially at 10 and 20 Hz, aminophylline increased tetanic force. The potentiating effect of aminophylline (100 microM) was reduced or eliminated in calcium-free Ringer containing 10 mM magnesium. We conclude that aminophylline, at therapeutic concentrations, enhances muscle contractility, and the enhancement is dependent on the presence of extracellular calcium. These findings support the concept that aminophylline is effective in improving respiration in humans with airway obstruction by enhancing diaphragmatic contractility.

Aminophylline↗
PubMed1988

Dual effects of theophylline on spontaneous transmitter release from frog motor nerve terminals.

Alkylxanthine drugs, such as theophylline, block adenosine receptors, inhibit phosphodiesterases and other enzymes, and cause the release of calcium from intracellular stores. Adenosine receptor blockade occurs at low micromolar concentrations of the drugs, while other effects occur in the millimolar concentration range. The effects of theophylline were tested on spontaneous transmitter release at the frog cutaneous-pectoris neuromuscular junction (NMJ). A change in the frequency, but not the amplitude, of miniature endplate potentials (mepps) was interpreted as a change in spontaneous transmitter release. In normal Ringer's, theophylline, at concentrations of 100 microM and 1 mM, theophylline had no consistent effect on spontaneous release. In contrast, theophylline produced dual effects on mepp frequency in hyperosmotic Ringer's. At 10 microM, theophylline depressed mepp frequency, while, at 100 microM and 1 mM, theophylline increased mepp rate. Since low micromolar concentrations of theophylline depressed spontaneous transmitter release, this action may result from adenosine receptor blockade and inhibition of a tonic, stimulatory effect of adenosine. This hypothesis was supported by the following experimental results: (1) Micromolar concentrations of theophylline reversed the effects of applied adenosine on neuromuscular transmission. (2) The inhibitory effect of theophylline was mimicked by 2 other alkylxanthines, 8-phenyltheophylline and 8-p-sulfophenyltheophylline. These drugs may be more specific adenosine receptor antagonists than theophylline. (3) The inhibitory effect of theophylline was mimicked by adenosine deaminase, an enzyme that breaks down and inactivates adenosine. (4) The depressant action of theophylline was masked by the addition of adenosine deaminase to the hyperosmotic Ringer's. Application of adenosine to the frog NMJ reduces spontaneous transmitter output.(ABSTRACT TRUNCATED AT 250 WORDS)

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1986

Dietary choline augments associative memory function in Limax maximus.

Previous clinical and experimental work has shown that increased dietary intake of choline elevates blood choline and brain acetylcholine levels. This change in neuronal acetylcholine concentration may augment learning and memory functions. We tested this prediction using the mollusc Limax maximus, an animal which can be readily conditioned to avoid food odors. In our experiments, initial learning of a food avoidance task was not augmented by the high choline diet. However, the duration of memory retention was prolonged. In previous studies, we have shown that intake of the choline enriched diet significantly increases blood choline and amplifies transmission at an identified cholinergic synapse in Limax. Together, these results support the involvement of cholinergic synapses in the memory retention mechanism.

Animals↗
PubMed1985

Characterization of tissue-derived macromolecules affecting transmitter synthesis in rat spinal cord neurons.

Rat spinal cord cells maintained in neuron-rich cultures were exposed to extracts of skeletal muscle or to medium conditioned by non-neuronal cells. The conditioned media enhanced neuronal acetylcholine (ACh) synthesis, choline acetyltransferase activity, and protein synthesis, and decreased gamma-aminobutyric acid (GABA) synthesis. Muscle extract prepared from newborn rats produced similar enhancements but did not depress GABA synthesis. Muscle extracts prepared from normal and denervated adult rat limbs contained relatively little activity. These results suggest that different molecular factors might mediate the effects on GABA and ACh synthesis. Gel filtration of conditioned media and muscle extracts revealed that all of these activities were confined to a macromolecular fraction with an apparent Mr of 40,000. These tissue-derived factors affecting neuronal protein and transmitter synthesis are in turn distinct from a neuronal survival-promoting factor obtained from serum (Kaufman, L. M., and J. N. Barrett (1983) Science 220: 1394-1396).

Acetylcholine↗
PubMed1984

Baclofen has a presynaptic action at the crayfish neuromuscular junction.

The action of baclofen, a GABA analog, was studied at the crayfish neuromuscular junction (NMJ). Baclofen depressed the amplitude of excitatory junction potentials (ejps) without affecting muscle input resistance and reduced the frequency of spontaneous miniature ejps without affecting their size. Thus, baclofen may mediate presynaptic inhibition by depressing transmitter release from the excitatory nerve. The site of baclofen's effect at the crayfish NMJ may parallel its site of action in the vertebrate nervous system.

Animals↗
PubMed1984

Acetylcholine turnover in an autoactive molluscan neuron.

We have studied acetylcholine (ACh) turnover at the cholinergic synapse between an identified motoneuron, the salivary burster (SB), and the muscle cells of the salivary duct (SD) in the terrestrial mollusk Limax maximus. Electrophysiological recordings were made of the SB action potentials and the SB-elicited junction potentials (JPs) on the SD. The amplitude of the JP was used as a measure of ACh release by the SB. The SB is an autoactive neuron that discharges 1 to 12 bursts of action potentials per min. During sustained bursting activity, the SB is able to maintain transmitter release for 18 hr even in the absence of exogenous choline. The size of SB-elicited JPs does not vary during 18 hr of activity. If the choline uptake blocker, hemicholinium-3 (HC-3; 20 microM), is present in the saline, transmitter release and JP size are depressed by about 30% after 14 hr of activity. Thus, the SB is partially dependent upon choline reuptake for maintained ACh synthesis and release. In high (9.45 mM)-potassium (K+) saline, the SB fired tonically at twice its average spike frequency. JP amplitude initially increased, then declined to an amplitude which was 60% of the initial level. The addition of 20 microM HC-3 to the high-K+ saline caused a 75 to 100% decrease in JP size within 30 min. Thus, during high-frequency tonic firing, the SB was primarily dependent on choline reuptake for ACh synthesis and release. After JP size had been reduced in high-K+ saline containing HC-3, the SB-SD synapse was returned to normal choline-free saline. The SB resumed bursting activity. JP amplitude gradually increased over the next 30 min. Thus, high-frequency firing in HC-3 had not depleted the SB of its entire endogenous store of choline or ACh. If the synapse was fatigued in high-K+ saline containing HC-3 and then placed in saline enriched with 300 microM choline, JP size increased within minutes. Thus, uptake of choline for ACh synthesis and release may be a more rapid process than mobilization of an endogenous transmitter store. Finally, the SB-SD synapse was fatigued in high-K+ saline containing HC-3. HC-3 was then removed from the saline. The SB maintained high-frequency tonic activity. JP size did not increase unless choline was added to the saline.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1982

Exogenous choline augments transmission at an identified cholinergic synapse in terrestrial mollusk Limax maximus.

1. A variety of pharmacological tests indicate that the neuromuscular junction between the salivary burster neuron (SB) and the salivary duct muscle (SD) in the terrestrial mollusk Limax maximus is cholinergic. These include the effects of curare, atropine, and hexamethonium. 2. Exogenously applied choline can act both presynaptically and postsynaptically at the synapse between the SB and SD. a) When the SB-SD synapse is bathed in 30 microM choline, there is no measurable direct postsynaptic effect at the SB-SD synapse. After several hours of choline incubation, however, an increase is observed in the size of SB-elicited junction potentials recorded from the SD. b) When the synapse is bathed in 300 microM choline, a short-term decrease is seen in the amplitudes of junction potentials (JPs) recorded from the SD. This effect is interpreted as competition between choline and acetylcholine (ACh) for postsynaptic receptor sites on the SD, since the response of the denervated SD to ACh is diminished in the presence of 300 microM choline. c) After several hours incubation in 300 microM choline, the amplitudes of JPs elicited by the SB on the SD increase. 3. The long-term effect of exogenous choline is blocked by the choline-uptake inhibitor, hemicholinium 3. 4. We conclude that exogenous choline is taken up by the presynaptic terminals of the SB and converted to ACh. Transmitter output rises with growing transmitter stores, producing an increase in the size of SB-elicited JPs recorded from the SD.

Acetylcholine↗
PubMed1982

Dietary choline augments blood choline and cholinergic transmission in terrestrial mollusk Limax maximus.

1. A radioenzymatic assay was used to determine the concentration of choline in the hemolymph of the terrestrial mollusk Limax maximus maintained on choline-enriched and choline-deficient diets. The levels of free choline in the slug's hemolymph varied with the availability of choline in the diet. The concentration of choline in the plasma of choline-enriched animals averaged 5.5 microM while the mean circulating choline level of choline-deprived slugs was 3.3 microM. The difference in choline levels between the two groups was statistically significant. 2. Neurophysiological measurements of transmission at the isolated cholinergic synapses between the salivary burster neuron (SB) and the salivary duct muscle (SD) showed that this synapse was sensitive to fluctuations in the external choline concentration within the physiological range. Increases in exogenous choline from 0.5 to 2.0 microM, from 2.5 to 5.0 microM, and from 5.0 to 15.0 microM were followed by increases in the amplitudes of SB-elicited junction potentials recorded from the SD by a focal extracellular electrode. 3. Thus, the SB-SD synapse is sensitive to the fluctuations in exogenous choline that can occur with a change in diet.

Acetylcholine↗