Diffusion of labelled substances through isolated rat diaphragm

An anti‐curare effect of hexamethonium at the mammalian neuromuscular junction

“…The diffusion coefficients calculated relative to that of gallamine are shown in parentheses. The diffusion coefficient of (+)-tubocurarine relative to gallamine when determined from conductivity measurements (Brooks & MacKay, 1971b) varied from 0-61 to 1-03. Because of the similarities in the diffusion coefficients of hexamethonium and (+ )-tubocurarine relative to that of gallamine when calculated from the molecular weight and from the experimentally determined half-recovery time, we conclude that the time constant of clearance of the receptors when the antagonists were washed out was determined by the diffusion of the drug from the synaptic cleft, and this confirms the conclusion of Brooks & MacKay.…”

Rate of onset and offset of neuromuscular block in the isolated rat diaphragm

“…The results presented here show that in these experiments the onset and offset of neuromuscular blockade by tubocurarine and gallamine are diffusion controlled. Experiments with [14C] sucrose have shown that the tortuosity factor for rat diaphragm decreases with time after excision of the muscle (Brookes & Mackay, 1971). It therefore seems likely that the increased rate of onset of blockade seen with successive applications of the same concentration of tubocurarine, is largely due to this decrease in tortuosity factor.…”

“…The time required to measure equilibrium blockade at five concentrations (for a dose-response curve) was at least 1 h for gallamine, and 2 h for tubocurarine. When the offset of action of the drug had been recorded the thickness of the tissue was measured and the parameters for the diffusion of ['4C] sucrose through the muscle interspaces were determined by methods described in another paper (Brookes & Mackay, 1971). In order to estimate the values of the tortuosity factors predicted from the rates of onset and offset of neuromuscular block the diffusion coefficients of the tubocurarine Onsets of action of tubocurarine (0.75 gg/ml) applied to an isolated rat diaphragm 30 min (A) and 150 min (B) after dissection of the muscle.…”

“…The record shows maximal isometric contractions elicited by alternate direct and indirect stimuli applied to the diaphragm at a total rate of four/minute. and gallamine cations in free solution at 360 C were taken to be 5-06 x 10-6 cm2/s and 5-86 x 10-6 cm2/s respectively (Brookes & Mackay, 1971).…”

“…The time required to measure equilibrium blockade at five concentrations (for a dose-response curve) was at least 1 h for gallamine, and 2 h for tubocurarine. When the offset of action of the drug had been recorded the thickness of the tissue was measured and the parameters for the diffusion of ['4C] sucrose through the muscle interspaces were determined by methods described in another paper (Brookes & Mackay, 1971 and gallamine cations in free solution at 360 C were taken to be 5-06 x 10-6 cm2/s and 5-86 x 10-6 cm2/s respectively (Brookes & Mackay, 1971).…”