7-OXO-PROSTACYCLIN AFFECTS THE ELECTROGENIC NA+ K+ PUMP IN MOUSE DIAPHRAGM FIBERS/

The effect of a stable prostacyclin derivative, 7-oxo-prostacyclin, on the electrogenic Na+/K+ pump in mouse diaphragm muscle was investigat ed. Resting membrane potentials of muscle cells were measured with gla ss microelectrodes. In fresh diaphragm preparations from 7-oxo-prostac yclin-pretreated mice (50 mu g . kg(-1) 7-oxo-prostacyclin i.p. 30-34 h prior to the experiment) resting membrane potentials were significan tly higher (-83.86+/-1.40 mV, mean+/-S.E.M.) than in control preparati ons (-70.73+/-1.07 mV). Ouabain at a concentration of 10(-4) mol . l(- 1) abolished this hyperpolarization (P<0.05). The electrogenic effect induced by addition of 5 mmol . l(-1) K+ to Na+-loaded muscles from 7- oxo-prostacyclin-pretreated animals was also enhanced (Delta resting m embrane potential = 21.73+/-3.13 mV) compared with that of the control s (Delta resting membrane potential = 18.36+/-1.29 mV). Ouabain antago nized the increase in electrogenicity of Nac-loaded diaphragms induced by 7-oxo-prostacyclin pretreatment (P<0.05). In contrast to control p reparations, no inhibition of the electrogenic effect induced by 10 mm ol . l(-1) Ca2+ ions in Na+-loaded muscles was observed in diaphragms from 7-oxo-prostacyclin-pretreated animals. In acute experiments with Nac-loaded muscles, where 10(-7) mol . l(-1) 7-oxo-prostacyclin was ad ded to the bath, resting membrane potential reached up to -100 mV. The electrogenic pump-induced increase in resting membrane potential amou nted to approximately 30 mV. This effect could be also abolished by 10 (-4) mol . l(-1) ouabain (P<0.05). The data indicate a stimulating eff ect of 7-oxo-prostacyclin on the electrogenic Na+/K+ pump and increase d tolerance of the skeletal Na+/K+ pump to ouabain and Ca2+.