title: Harmaline distribution in single muscle fibres and the inhibition of sodium efflux.
abstract: Harmaline, a known inhibitor of the (Na+ + K+)-ATPase in cell membranes, inhibited 50% of the 22Na efflux from barnacle muscle fibres at an extracellular concentration of 2.4 mM. Injected harmaline inhibited 50% of the efflux at an estimated intracellular concentration of about 8 mM . kg-1, assuming complete equilibration with no binding. Total fibre harmaline was measured in separate fibres by ultraviolet spectrophotometry. Fibres in 3 mM harmaline saline accumulated harmaline with a half-time of 17 min and a final total fibre concentration of 6-12 mM . kg-1. In harmaline-free saline this accumulated harmaline was lost exponentially with a half-time of 35 min; injected harmaline was lost exponentially from fibres with a half-time of 50 min. It is proposed that harmaline crosses the fibre membrane as the uncharged base and that its apparent accumulation against a concentration gradient is mainly due to intracellular binding with an additional contribution from a transmembrane ph gradient. It is concluded that, in fibres exposed to harmaline saline, the intracellular concentration can reach a sufficiently high value, as judged from the results of the injection experiments, to inhibit Na+ efflux at an interior-facing site on the fibre membrane. In contrast, harmaline appears to inhibit the Na+-dependent uptake of L-glutamate at an extracellular site.
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism; D006246:Harmaline / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D001468:Thoracica
chemical_list: D000470:Alkaloids; D005971:Glutamates; D010042:Ouabain; D012964:Sodium; D006246:Harmaline