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Biomedical subjects

W A Wilson

Publications and source records attributed to W A Wilson.

At least 127 records · Page 7Linked to original sources
PubMed1985

Induction of epileptiform activity in hippocampal slices by trains of electrical stimuli.

In this paper we present an in vitro model of epileptogenesis based on electrical stimulation rather than pharmacological or ionic manipulations. Hippocampal slices given a series of stimulus trains similar to those used in kindling exhibited 3 types of epileptiform activity in CA3: afterdischarges immediately following the trains; spontaneous bursts of multiple population spikes; and bursts triggered by single stimuli. The afterdischarges and spontaneous bursts may be comparable to those seen in vivo during kindling; also, the progression of these features in this model was similar to their progression during kindling. All epileptiform activities were long-lasting, persisting for up to 3.5 h following the last train. This stimulus train-induced population bursting should be valuable as an acute model of hippocampal epileptogenesis, and may also help elucidate hippocampal participation in the kindling process.

Action Potentials↗
PubMed1985

The ionic mechanism of the slow outward current in Aplysia neurons.

A slow outward current associated with spike frequency adaptation has been studied in the giant Aplysia neurons R2 and LP1. The current was observed during 60-s voltage clamp commands to potentials just below spike threshold. The slow outward current shows a marked voltage dependence at membrane potential less negative than -40 mV. The slow outward current is associated with increased membrane conductance. The K+ sensitivity of the slow outward current was studied by varying the extracellular K+ concentration and also by measuring potassium efflux with a K+-sensitive electrode. Both procedures indicated that the slow outward current was K+ dependent. Tail currents following the activation of the slow outward current were examined. They were shown to have a similar potassium sensitivity as the slow outward current and had a reversal potential near the potassium equilibrium potential for these cells. The sensitivity of the slow outward current to known blockers of K+ currents, tetraethylammonium and 4-aminopyridine, was tested. The sensitivity was much less than that reported for other K+ currents. The sensitivity of the slow outward current to changes of the extracellular concentrations of Na+ and Cl- ions, as well as electrogenic pump inhibitors, was tested. The results indicate that the slow outward current is much less sensitive to these changes than to the manipulations of the extracellular K+ ion concentration. We tested the sensitivity of this current to manipulations of intracellular and extracellular Ca2+ ion concentrations. We found that the current persisted at a slightly reduced level in the absence of extracellular calcium or in the presence of calcium blocking agents, cobalt and lanthanum. Intracellular injection of the calcium chelator EGTA at a concentration sufficient to block the Ca2+-dependent K+ current, seen after a brief (1.4-s) burst of action potentials, had minimal effects on the slow outward current. Procedures thought to increase intracellular Ca2+ were tested. We found that exposure of the cell to solutions containing elevated Ca2+ concentrations for prolonged periods increased the slow outward current. Also, treatment with drugs thought to elevate intracellular Ca2+ increased the slow outward current. In conclusion, the slow outward current results from an increased K+ conductance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Comparison of the effects of diphenylbarbituric acid, phenobarbital, pentobarbital and secobarbital on GABA-mediated inhibition and benzodiazepine binding.

We utilized biochemical and electrophysiological methods to compare the effects of anesthetic and anticonvulsant barbiturates on gamma-aminobutyric acid (GABA) receptor-coupled responses. Biochemical analysis involved barbiturate regulation of the affinity of a radiolabeled benzodiazepine for benzodiazepine receptors. The electrophysiological method involved regulation of somatic recurrent inhibition of CA1 pyramidal cells in the hippocampal slice preparation. We found that anesthetic (secobarbital and pentobarbital) but not anticonvulsant (phenobarbital and diphenylbarbituric acid) barbiturates significantly enhanced GABA receptor-coupled responses in both the biochemical and electrophysiological preparations. The results indicate that the anticonvulsant actions of barbiturates may not depend on their ability to enhance GABAergic neuronal activity.

Animals↗
PubMed1985

Suppression of repetitive firing of neurons by diphenylbarbituric acid.

A slow outward current has been demonstrated in Aplysia giant neurons which serves to suppress repetitive firing. The barbiturates phenobarbital and pentobarbital enhance the slow outward current and the suppression of repetitive firing. In this study, the effects of diphenylbarbituric acid, which shows anticonvulsant activity in mice and rats but possesses minimal sedative properties, were tested on slow outward current and firing behavior. Diphenylbarbituric acid enhances slow outward current and suppresses repetitive firing at lower concentrations than phenobarbital and pentobarbital. Because diphenylbarbituric acid is effective at enhancing slow outward current but does not produce sedation, this property of barbiturates is apparently not associated with the sedative properties of these drugs, but rather is important for the anticonvulsant effects.

Adaptation, Physiological↗
PubMed1985

Barbiturate-induced alterations in the kinetic parameters of slow outward current in Aplysia giant neurons.

Regulation of spike frequency adaptation has been postulated to be a neuronal mechanism of action of the barbiturates (Zbicz and Wilson, 1981). A barbiturate sensitive slow outward current is present in Aplysia giant neurons, and this current is very effective at regulating adaptation. In the current study a quantitative method of determining the effect of barbiturates was developed using a single-electrode voltage clamp. This method, tail current analysis, involved measuring the exponential decay of the slow outward current at the end of a depolarizing voltage-clamp command. The tail currents were made up of two decay phases with average half-times of 7 and 70 sec, and the tail current amplitude accurately reflected the magnitude of slow outward current. Barbiturates were found to cause a concentration-related, saturable and stereospecific increase in one component of the tail currents, the amplitude of the slow phase. With moderate concentrations of barbiturates there were no changes in the other parameters describing the exponential decay current. The rank order of potency of barbiturates for the enhancement of slow outward current was not well correlated with the lipid solubility of these drugs, indicating that slow outward current enhancement is not due to a nonspecific mechanism, but rather may be receptor mediated.

Action Potentials↗
PubMed1984

Splenic function in sickle cell disease in the Eastern Province of Saudi Arabia.

The sickle cell disease that occurs in the Eastern Province of Saudi Arabia is reported to be clinically benign. It is biochemically characterized by high levels of fetal hemoglobin. Twenty-four Saudi patients with sickle cell disease were compared with 22 American patients. As a group, the Saudi patients were less anemic and had less hemolysis, microcytic RBC, and much higher levels of Hb F. Splenic function was assessed by enumeration of pocked RBC. Seventeen Saudi patients had low numbers of Pk RBC, indicating normal or nearly normal splenic function, whereas all American patients had markedly decreased splenic function and high numbers of Pk RBC. Low levels of Pk RBC were strongly associated with high levels of Hb F. The genetic basis of the milder sickle cell disease in Saudi Arabia has not been elucidated, but may involve multiple genetic factors. Although the sickle cell disease in Arab patients of eastern Saudi Arabia is often less severe than that in America, it is far from "benign," and some patients have severe clinical courses similar to those in patients in the West.

Adolescent↗
PubMed1984

Association of HLA-DR7 with both antibody to SSA(Ro) and disease susceptibility in blacks with systemic lupus erythematosus.

The relationship between HLA-DR antigens and various specific antinuclear antibodies was studied in 28 unselected black Americans with systemic lupus erythematosus (SLE). Anti-SSA(Ro) occurred with high frequency (61%) but was not associated with specific clinical features of SLE. HLA-DR7 was strongly associated with anti-SSA antibody; it was present in 13/17 patients with anti-SSA (76%) and 1/11 patients without it (9%). HLA-DR7 occurred in 14/28 of all SLE patients (50%) compared with 17% of 137 local controls (p corrected, less than 0.005). This association of HLA-DR7 with both susceptibility to SLE and a high frequency of anti-SSA antibody suggests a genetic link between the presence of anti-SSA antibody and susceptibility to SLE in the population studied.

Adolescent↗
PubMed1984

Dopamine reduces slow outward current and calcium influx in burst-firing neuron R15 of Aplysia.

Dopamine's effect on calcium influx into the bursting neuron, R15, of Aplysia californica was tested by tail current measurements and by measurement of absorbance of intracellular Arsenazo III, a calcium-sensitive indicator. Slow outward tail currents were elicited by subthreshold depolarization in voltage clamp and were demonstrated to be dependent upon transient increases in intracellular calcium activity, (Ca)i), using calcium-free seawater, calcium blockers (Mn2+ and La3+), and intracellular injection of EGTA. Dopamine reduces these tail currents as it reduces the slow inward current. Next, the transient elevations of (Ca)i accompanying subthreshold depolarization were measured directly in Arsenazo III-loaded neurons. Dopamine did not reduce the rise in (Ca)i measured in the soma during depolarization. However, when absorbance of the axodendritic region was monitored, dopamine did reduce calcium influx. Voltage monitoring in the axon indicated that the reduced calcium influx could not simply be ascribed to altered space clamp. In keeping with the apparent axodendritic location of dopamine action, isolation of the soma by ligation of the axon markedly reduced the dopamine response. Dopamine seems to reduce calcium influx into R15, but this effect is topographically limited to nonsomatic membrane, an area of the neuron not usually monitored in optical studies of (Ca)i.

Animals↗
PubMed1983

Barbiturate effects on acetylcholine-activated channels in Aplysia neurons.

The effects of pentobarbital, phenobarbital, amobarbital, and diphenylbarbituric acid were studied by examining the average lifetime and conductance of acetylcholine-activated sodium channels in Aplysia neurons. Although none of the barbiturates tested modified the conductance of single-ion channels, pentobarbital and amobarbital had profound effects on channel lifetime. In the absence of barbiturate, relaxations in response to voltage jumps during steady-state current responses to acetylcholine have a single-exponential time course. In the presence of pentobarbital (75-500 microM), current relaxations consist of two exponential components that take the same direction as control relaxations. The faster component becomes faster and relatively larger at higher pentobarbital concentrations, while the slower component always has the same time constant as control. These results are not consistent with a sequential model of channel blockade described for local anesthetics, in which blocked channels must become unblocked before channel closure can occur. Kinetic data are better explained by a cyclic model in which blocked channels have the same probability of closing as nonblocked channels. Alternatively, the results can also be explained by a two-site model in which one binding site regulates the susceptibility of channels to the effects of the barbiturate, whereas occupation of the second site determines the extent of changes in channel lifetime. The effects of amobarbital were qualitatively similar to those of pentobarbital, while phenobarbital and diphenylbarbituric acid did not alter current relaxations at similar concentrations.

Acetylcholine↗
PubMed1981

Use of the single electrode voltage clamp to perform noise and relaxation studies of acetylcholine-activated channels in Aplysia neurons.

The single electrode voltage clamp has been used to perform fluctuation analysis ("noise" analysis) and relaxation experiments in order to study the average lifetime and conductance of ACh-activated sodium channels in Aplysia neurons. Measured values of average channel lifetime, which is approximately 20 msec at --80 mV and 11 degrees C, and elementary conductance, which is approximately 8 pS, are consistent with previously published results using two electrode clamping. The frequency response of the clamp was evaluated to determine its capabilities and limitations for the study of membrane currents. Sinusoidal currents injected into a voltage-clamped model membrane to simulate the frequency components of membrane noise are accurately reproduced at frequencies up to 500 Hz. Following a voltage clamp command, the new membrane potential is established in less than 2 msec, and current relaxations recorded after that time can be used to determine average channel lifetime. Since the frequency response of the clamp is much greater than the average lifetime of ACh-activated channels in Aplysia neurons, the single electrode voltage clamp is comparable to conventional two-electrode systems for investigating the properties of these channels, and may also be useful in other systems in which the time course of membrane currents is much slower than the frequency response of the clamp.

Acetylcholine↗
PubMed1981

Serum urate concentrations in homozygous sickle cell disease.

Serum and urinary urate concentrations were studied in 44 patients with homozygous sickle cell (SS) disease, and in 27 controls with normal haemoglobin. Hyperuricaemia (>0.39 mmol/l (6.5 mg/100 ml)) occurred in 41% of SS patients and inversely correlated with renal urate clearance but not with indices of bone marrow turnover. Higher serum urate concentrations occurred in patients with proteinuria, probably due to associated tubular damage. Higher serum urate concentrations and lower urate clearance occurred in males compared to females.

Adolescent↗
PubMed1981

Pharmacological studies of a novel dopamine-sensitive receptor mediating burst-firing inhibition of neurosecretory cell R 15 in Aplysia californica.

Burst-firing activity of neuron R 15 in the abdominal ganglion of Aplysia californica is inhibited by dopamine (DA) (50-500 microM). By using voltage clamp analysis of agonist-induced reduction of inward current and bath application of pharmacological agents, the agonist and antagonist specificity of the receptor mediating burst-firing inhibition in this cell was studied. The phenethylamine compounds DA, epinine, (-)-norepinephrine, (+)-norepinephrine, (-)-epinephrine, (+)-epinephrine and (-)-phenylephrine are active at similar concentrations. DA analogs 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene HBr and 2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene HBr are active, whereas apomorphine, piribedil, (3,4-dihydroxyphenylamino)-2-imidazoline HCl and RU 24213 are inactive. DA-mediated inhibition of burst-firing is not antagonized by neuroleptics or certain adrenergic antagonists. Antagonism is seen with dihydroergotamine, lysergic acid diethylamide, ergonovine and other ergot alkaloids and the complex nature of this antagonism is discussed in detail. The specificity of this receptor for agonists and antagonists is compared to DA and adrenergic receptors from mammalian and other invertebrate tissues. We conclude that this DA-sensitive receptor mediating burst-firing inhibition of cell R 15 in Aplysia californica is very different from DA and adrenergic receptors.

Animals↗