Transmembrane movement of lithium ions in isolated sheep heart Purkinje fibres.
The many routes by which Li can cross the cardiac sarcolemma were examined using Li-selective microelectrodes. In the presence of 70 mmol/l extracellular Li there was a rapid increase in intracellular Li activity (aiLi) equivalent to an influx of 0.45 mmol/l/min (or 2.1 pmol/cm2.s). Depolarisation (voltage-clamp or high [K]O) had no significant effect on the rate of aiLi increase, or recovery on removal of LiO. Following addition of 20 mmol/l [Li]O to the normal Tyrode, the rate of aiLi increase was stimulated by 49.7% by removal of extracellular Mg. However Li entry was inhibited by SITS (100 mumol/l) by 20.6%; tetrodotoxin (10(15)g/ml) 20.0%; caesium (2 mmol/l) 22.5%; verapamil (20 mumol/l) 14.3%; and manganese (1 mmol/l) 37.6%. With 5 mmol/l [Li]O, aiLi stabilized at 2.3 mmol/l, i.e. much lower than expected assuming passive distribution of Li (predicted level 61 mmol/l), implying active extrusion of Li from the cells. This stable level of Li was not significantly affected by short exposures to strophanthidin, bumetanide, or ethyl isopropylamiloride, but was decreased by increasing the [Ca]O or adding manganese. The aiLi was increased on removal of [Na]O or addition of phloretin (100 mumol/l) suggesting that NaO-Lii exchange helps to maintain a low aiLi. The removal of KO produced an increase in aiLi. This effect was inhibited by strophanthidin, suggesting Li can enter via the Na/K pump in K-free conditions.
Gow
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IF
University Medical School, Edinburgh, UK.
Ellis
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D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008094:Lithium / Q000493:pharmacokinetics*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008839:Microelectrodes; D011690:Purkinje Fibers / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep; D013779:Tetrodotoxin / Q000494:pharmacology
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D013779:Tetrodotoxin; D008094:Lithium