The actions of 5-hydroxytryptamine on isolated skeletal muscle preparations

The effects of 5-hydroxytryptamine (5HT) on the mouse phrenic nerve--hemidiaphragm and frog sartorius muscle preparations were studied using twitch tension and intracellular recording methods. Between 1--7.5 mM 5HT transiently augmented the twitch response of the diaphragm to indirect, but not direct, stimulation. Above 5 mM 5HT the augmentation was followed by a concentration-dependent twitch blockade. The blockade was more apparent in anticholinesterase-treated preparations, and was seen to a lesser extent in directly stimulated muscles. Intracellular recording from diaphragm muscles revealed that 5HT depressed the amplitudes of both miniature endplate potentials (m.e.p.p.s.) and endplate potentials (e.p.p.s.), this effect being more pronounced in the presence of neostigmine. 5HT also greatly prolonged the duration of the e.p.p.s. In the sartorius muscles, 1--5 mM 5HT slowed and depressed action potentials. It is suggested that 5HT facilitates transmission by an anticholinesterase action and inhibits by blockade of receptor ion channels.