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Biomedical subjects

G J Evans

Publications and source records attributed to G J Evans.

9 recordsLinked to original sources

Role of cyclic AMP dependent protein kinase in cannabinoid receptor modulation of potassium "A-current" in cultured rat hippocampal neurons.

Cannabinoid receptor agonists have been previously shown to enhance a potassium A-current (IA) in cultured rat hippocampal neurons. This effect has been further demonstrated to be dependent on G-protein linkage to adenylyl cyclase and levels of intracellular cyclic AMP (cAMP). The present study extends this analysis to the involvement of cAMP-dependent protein kinase (PKA) in this cascade. Specific activators and inhibitors of PKA were shown to have differential effects on the voltage dependence of IA. Specific activators of PKA produced a negative shift in voltage dependence of IA, whereas PKA inhibitors produced a positive shift in IA voltage dependence, the latter similar to that effected by the cannabinoid agonist WIN 55,212-2. Although the negative shift in IA induced by PKA stimulation could be reversed by PKA inhibitors, the positive shift produced by the PKA inhibitors alone was only 50-60% of the cannabinoid-produced shift in IA voltage dependence. This partial effect of PKA inhibition was confirmed by biochemical assays in the same cultured neurons that showed a similar 50-60% decrement in in vitro protein phosphorylation produced by PKA inhibitors. Results are discussed in terms of a diffusible second messenger linkage of the cannabinoid receptor to the A-current channel via the role of protein phosphorylation in modulation of IA.

Animals

A novel, calcium-induced triphasic current response in silent, non-bursting Aplysia neurons.

The iontophoretic injection of Ca2+ ions into voltage-clamped, silent neurons of Aplysia californica results in a prolonged, triphasic current response. This response consists of: a tetraethylammonium-sensitive outward current during the injection; followed by an inward current 10-30 s after the end of the injection; and finally a long, slowly increasing outward current that lasts for several minutes before returning to baseline.

Animals

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

Septal inhibition of aversive emotional states.

Two experiments were carried out to test the proposition that electrical stimulation of the septal region of the cat has the capacity to inhibit aversive emotional states. In the first experiment the source of aversive stimulation was electrical stimulation of various hypothalamic regions. The results were: (1) The animals would perform a learned response in order to obtain septal stimulation only if given concomitant aversive hypothalamic stimulation. (2) If septal stimulation was omitted the animal showed a conventional extinction effect. (3) If non-aversive hypothalamic stimulation was substituted for aversive stimulation the animal did not perform to obtain septal stimulation. In the second experiment a side preference was influenced by septal stimulation only when carbachol was administered to the hypothalamus, otherwise septal stimulation was neutral. It was concluded that these data provide evidence of an emotion inhibitory function of activity of the septal region.

Animals

The elderly in the wrong unit.

Patients over 65 admitted from an area of North London forming the overlapping part of the catchment areas of a geriatric unit and a psychiatric unit were studied, with particular reference to misplacement in the inappropriate hospitals service and its consequences.The incidence of misplacement found was much lower than previously reported. In the geriatric unit 2.2% of admissions were definitely and 6.0% were probably misplaced. In the psychiatric unit 6.2% were definitely and a further 8.4% were probably misplaced. Misplacement did not materially affect the outcome. The striking differences that were found between the patterns of death and discharge in the geriatric and psychiatric units were determined principally by the type of illness leading to admission.The frequent coexistence of mental and physical disorders in the elderly patient, which this study confirms, indicates the need for further development of effective liaison at a local level between the geriatric, psychiatric, and social services.

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