Attenuation of rat diaphragm low-frequency fatigue by vanadate in vitro

Sodium vanadate inhibits protein tyrosine phosphatases, including in skelet al muscle. Vanadate increases contractile force of airway, vascular and gas trointestinal smooth muscle, The present study tested the hypothesis that v anadate augments skeletal muscle contractility. Rat diaphragm muscle strips (n = 26 from 12 animals) were studied in vitro at 37 degrees C. Muscles co ntracted isometrically while stimulated supramaximally with one of two prot ocols: 30 min of continuous 0.1 Hz stimulation, or 5 min of intermittent 20 Hz stimulation (duty cycle 0.33). Vanadate (500 mu M)-treated muscle strip s were compared with untreated muscle. Vanadate did not affect force or iso metric twitch kinetics of otherwise quiescent muscle. During prolonged 0.1 Hz stimulation, force of control muscles declined by 17 +/- 4% over 30 min, whereas muscles incubated with vanadate maintained force virtually unchang ed. Force over time was significantly greater with than without vanadate (P = 0.03), with values being significantly different during the last 10 min of the 30 min stimulation period. In the absence of vanadate force declined at a rate of similar to 0.6% per min. whereas with vanadate the rate of fo rce decline was less than 0.1% per min (P < 0.02). During intermittent 20 H z stimulation, the degree of force decline was not affected by vanadate at any time over a course of 5 min. Isometric contractile kinetics were not al tered by vanadate during either 0.1 or 20 Hz stimulation. These data sugges t that vanadate ameliorates low- but not higher-frequency fatigue in diaphr agm, suggesting a role for protein tyrosine phosphorylation in the regulati on of muscle fatigue resistance, (C) 1999 Elsevier Science B.V, All rights reserved.