Diazepam blockade of repetitive action potentials in skeletal muscle fibres. A model of its membrane action.
Diazepam inconcentrations of 10(-6) and 10(-5) M effectively blocks trains of action potentials (AP) in individual rat diaphragm muscle fibres 'in vitro'. Single APs, evoked and recorded intracellularly with double microelectrodes, were not affected by diazepam. Trains of APs, evoked in diaphragm fibers in a SO42-- -medium (Cl-- -free), were not affected by diazepam. Diazepam decreased the dependence of the membrane resting potential of muscle cells in chloride media on elevated external potassium whereas no effect was observed in SO42-- --Cl-- -free saline. Similar to in the rat diaphragm, diazepam blocked the trains of AP of individual muscle fibres in the frog sartorius muscle (Cl-- -medium). Diazepam did not affect the spontaneous fibrillatory APs recorded extracellularly from rat gastrocnemius muscles 10 days after denervation. Diazepam apparently increases the resting permeability of the muscle fibre memebrane for chloride ions. In the presence of the drug, the higher permeability for Cl- diminishes the depolarization caused by the potassium released and accumulated in the vicinity of the membrane in the course of AP. The muscle fibre membrane thus does not respond by repetitive activity when partially depolarized and only one AP can be evoked when diazepam is present. It is suggested that similar changes in Cl-- permeability may occur in brain excitable structures after diazepam administration and may account for some of the therapeutic effects of the drug.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008564:Membrane Potentials / Q000187:drug effects; D008959:Models, Neurological; D009132:Muscles / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D013779:Tetrodotoxin / Q000494:pharmacology
D002712:Chlorides; D013779:Tetrodotoxin; D003975:Diazepam; D011188:Potassium