Effects of 6-mercaptopurine treatment on the membrane potentials of rat skeletal muscle fibers
| Autor: | Nick Sperelakis, Frederic R. Alleva, Tibor Balazs, Michael S. Forbes, Phyllis Clouva-Molyvdas |
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| Rok vydání: | 1985 |
| Předmět: |
Male
medicine.medical_specialty Physiology Action Potentials Biology Ouabain Membrane Potentials Physiology (medical) Internal medicine medicine Animals Myocyte Pharmacology Membrane potential Mercaptopurine Muscles Rats Inbred Strains Depolarization General Medicine Rats Kinetics Microscopy Electron Electrophysiology Endocrinology Animals Newborn Female Sodium-Potassium-Exchanging ATPase Myofibril Caudofemoralis Microelectrodes Intracellular medicine.drug |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 63:1271-1278 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/y85-211 |
| Popis: | 6-Mercaptopurine (6-MP), injected daily (2 mg/kg s.c.) into Sprague–Dawley rats during the first 3 weeks of life, causes atrophy in muscles of the hindquarters beginning at 4 months of age. The extensor digitorium longus (EDL) muscles from 24 rats injected with 6-MP and 23 saline-injected controls, 6–18 months of age, were studied. Electron microscopy showed a number of abnormalities in the EDL muscle of 6-MP-treated rats, such as myocytes with atypical ultrastructure (including disorganized myofibrils) adjacent to structurally normal cells. Membrane potentials (Em) were measured in the isolated EDL and in the caudofemoralis (CF) muscle in situ. The mean Em of fibers in the EDL of 6-MP-treated rats (−61.1 ± 0.7 (SE) mV) was lower than that of the control rats (−69.7 ± 0.6 mV). The same was true for the fibers of the CF muscle (−64.9 ± 1.5 mV for 6-MP-treated fibers vs. −71.6 ± 1.3 mV for controls). The contribution of the electrogenic pump potential to Em (± ouabain) was similar in 6-MP-treated and control rats, and therefore could not account for the depolarization observed in 6-MP-treated rats. This depolarization was not due to a decreased intracellular K+ concentration. The Na+:K+ permeability ratio (PNa/PK) was higher in the 6-MP-treated rats and could account for the decrease in Em. The action potentials (APs) of 6-MP-treated rats (elicited from the natural Em of the fiber) had lower maximum rate of rise [Formula: see text] (330 ± 20 vs. 391 ± 17 V/s in controls), and lower amplitude (65.1 ± 2.9 vs. 73.3 ± 1.8 mV). When hyperpolarized to −90 mV before eliciting the AP, fibers from 6-MP-treated rats had depressed [Formula: see text] (382 ± 19 vs. 511 ± 21 V/s in controls), depressed AP amplitudes (97.0 ± 2.1 vs. 105.1 ± 1.6 mV), and prolonged duration at 50% amplitude (APD50) (0.66 ± 0.03 vs. 0.60 ± 0.02 ms). These data demonstrate definite electrophysiological and ultrastructural abnormalities in the EDL muscle of 6-MP-treated rats, resembling those observed in murine muscular dystrophy. |
| Databáze: | OpenAIRE |
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