PubMed Health⌕ Search

Biomedical subjects

R O Edeson

Publications and source records attributed to R O Edeson.

24 records · Page 2Linked to original sources

Verapamil alters the amplitude and time course of miniature endplate current.

The effect of verapamil on neuromuscular transmission was examined by recording miniature endplate currents (mepcs) in voltage-clamped frog sartorius muscle fibres. In the presence of 100 microM verapamil, the amplitude and time constant of decay of the mepcs (tau D) were reduced to 68% and 55% of control respectively, and the normal voltage dependency of tau D was decreased. Part of the decrease in amplitude of the mepc was independent of changes in tau D because, on washout, recovery of tau D was more rapid than that of amplitude, and in some cells smaller concentrations of verapamil (1 and 10 microM) decreased amplitude without affecting tau D. Evidence of open and closed channel blockade by verapamil (5-20 microM) was obtained from ionophoretic end-plate current trains and it is proposed that these effects are mediated via an allosteric mechanism.

Animals↗

Numerical simulation of miniature endplate currents.

A FORTRAN computer program is described which enables solution of a set of partial differential equations describing synaptic transmission, including neurotransmitter diffusion, binding to receptors on the postsynaptic membrane with subsequent formation of open ion-conducting channels, and hydrolysis. Integration is performed with a widely available package (PDETWO), and flexibility is achieved through use of 6 user-specified routines. The reliability of solution was checked by comparison with an analytic solution for a diffusion-only model. Application of the program is illustrated with an analysis of miniature endplate current rise times.

Acetylcholine↗

Systematic mapping of descending inhibitory control by the medulla of nociceptive spinal neurones in cats.

Inhibition descending the spinal cord from the medullary brainstem was systematically mapped in two dimensions in anaesthetized cats. Fifty-four ipsi- and contralateral sites and 27 ipsilateral sites were electrically stimulated with concentric bipolar or with monopolar electrodes, respectively, whilst extracellularly recording firing of dorsal horn neurones to noxious heat. Effective bipolar stimulation, but not monopolar stimulation caused gross lesions at the stimulated sites. There were 3 ipsilateral sites at which descending inhibition was evoked with the smallest stimuli. These areas corresponded to nucleus raphe magnus, nucleus reticularis magnocellularis and the lateral tegmental field. Contralateral stimulation was as effective or more effective than ipsilateral stimulation. The inhibition of dorsal horn neurones was not due to the cardiovascular changes which sometimes accompanied stimulation of the brainstem. The data are discussed in relation to the analgesia which results from stimulating these areas of the brainstem.

Animals↗

The relative significance of spinal and supraspinal actions in the antinociceptive effect of morphine in the dorsal horn: an evaluation of the microinjection technique.

Large quantities of morphine injected directly into the brainstem of spinal anaesthetized cats inhibited the noxious heat-evoked excitation of dorsal horn neurones. The amounts required were similar to those that were required intravenously in cats with the spinal cord intact or transected. When the spinal cord was intact the amount of morphine microinjected into the brainstem required to inhibit the excitation of dorsal horn neurones was about ten fold less than it was in spinal animals. It is concluded that large, but not small doses of morphine microinjected into the brainstem can exert effects on the spinal cord after first entering the circulation. The effects of small doses are attributed to a local action in the brainstem which causes inhibition of spinal neurones either by activating descending inhibitory neuronal systems or by liberating endogenous substances which reach the spinal cord via the cerebro-spinal fluid. The concentrations of morphine achieved at various distances from the site of injection by the microinjection of microgram quantities and the time courses of the concentration changes were calculated from diffusion equations, assuming diffusion coefficients of 3 or 5 X 10(6) cm2 s-1. The curves obtained closely approximated those obtained experimentally. The concentrations achieved at distances up to 2 mm from the site of injection of 10 micrograms of morphine were calculated to exceed 10(-4)M and the time-courses of these concentration changes were compatible with the time course of inhibition of spinal neurones, or the production of analgesia after microinjection. Such concentrations are vastly in excess of those achieved in the brain after the systemic administration of morphine in analgesic doses. It is concluded that the local effects in the brainstem produced by the microinjection of microgram quantities of morphine have no relevance to the mechanism of analgesia produced by systemic administration.

Animals↗

Anomalous action of tubocurarine in the tibialis anterior muscle of the cat.

Low dose infusion of tubocurarine (20 micrograms/kg per min) causes an increase in muscle contraction in tibialis anterior of the cat. Tibialis anterior muscle of 13 adult cats was indirectly stimulated via the sciatic nerve using a square wave pulse of 0.2 ms duration and supramaximal voltage at 0.06 Hz. The increase is from 5-133% of control with a mean of 36%. This is sustained for a mean of 97 min, if the infusion is ceased when maximum potentiation is achieved. Duration of potentiation is decreased by increasing the frequency of stimulation. The potentiation occurs in the presence of either rising or falling concentrations of tubocurarine, and continuing the infusion results in neuromuscular blockade. One explanation of these observations is that low dose tubocurarine may interfere with presynaptic negative feedback control of acetylcholine release.

Animals↗

Potentiation by gentamicin of non-depolarizing neuromuscular block in the cat.

Gentamicin 1-5 mg/kg was injected into 14 anaesthetised cats in the presence of a constant, partial, non-depolarizing neuromuscular block. Twitch response in tibialis anterior was significantly depressed from 83% to 71% of control by a dose of 1.0 mg/kg. In soleus the same dose reduced twitch response from 76% to 71%. After a cumulative dose of 10 mg/kg twitch response in tibialis anterior and soleus was 34% and 37% of control respectively. Calcium chloride 20 mg/kg restored twitch response to 66% in both muscles. Smaller doses of calcium chloride caused partial reversal which was maintained for five minutes in only 50% of instances.

Animals↗