6-Mercaptopurine Treatment Affects the Membrane Potentials of Rat Skeletal Muscle Fibers
| Autor: | Frederic R. Alleva, Phyllis Clouva-Molyvdas, Michael S. Forbes, Nicholas Sperelakis, Tibor Balazs |
|---|---|
| Rok vydání: | 1986 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Health Toxicology and Mutagenesis Action Potentials 010501 environmental sciences Toxicology 01 natural sciences Permeability Ouabain Membrane Potentials 03 medical and health sciences Internal medicine medicine Animals Myocyte Fiber Myopathy 0105 earth and related environmental sciences Membrane potential 030102 biochemistry & molecular biology Mercaptopurine Chemistry Muscles Public Health Environmental and Occupational Health Rats Inbred Strains Depolarization Anatomy Muscular Dystrophy Animal Rats Electrophysiology Endocrinology Animals Newborn Potassium medicine.symptom Caudofemoralis medicine.drug |
| Zdroj: | Toxicology and Industrial Health. 2:81-97 |
| ISSN: | 1477-0393 0748-2337 |
| DOI: | 10.1177/074823378600200210 |
| Popis: | 6-Mercaptopurine (6-MP) was injected daily (2 mg/kg sc) into 24 Sprague-Dawley rats during the first three weeks of life. There were 23 saline-injected control animals. Atrophy of the muscles of the hindquarters in the 6-MP-treated rats began at about 4 months of age. The membrane potentials (Em) of the isolated extensor digitorum longus (EDL) and the caudofemoralis (CF) muscle (in situ) were measured with intracellular microelectrodes at 6-18 months of age. It was found that there was a wide spectrum of fibers with respect to electrical abnormalities in the 6-MP-treated muscles, some fibers having perfectly normal parameters. However, the mean resting Em of fibers in the EDL muscle of 6-MP-treated rats (-61.1 +/- 0.7 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). Experiments done in the presence and absence of ouabain indicated that the contribution of the electrogenic pump potential to Em was similar in 6-MP-treated and control rats, and therefore could not account for the depolarization observed in 6-MP-treated rats. The data also demonstrated that 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 decreased resting Em. The APs of 6-MP-treated rats (elicited from the natural Em of the fiber) had more fibers with a lower maximum rate of rise (+Vmax) (330 +/- 20 vs 391 +/- 17 V/sec) and lower amplitude (65.1 +/- 2.9 vs 73.3 +/- 1.8 mV) than in the control muscles. When hyperpolarized to -90 mV before eliciting the AP, fibers from 6-MP-treated rats still displayed depressed AP rates of rise (+Vmax of 382 +/- 19 vs 511 +/- 21 V/sec in controls), depressed AP amplitudes (97 +/- 2.1 vs 105 +/- 1.6 mV in controls) and slightly prolonged duration at 50% amplitude (APD50) (0.66 +/- 0.03 vs 0.60 +/- 0.02 sec in controls). These electrophysiological alterations produced by this chemically-induced myopathy are similar to those observed in murine muscular dystrophy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|