Received July 13, 2005
Revised August 15, 2005
Accepted after revision August 17, 2005
CAFFEINE ADMINISTRATION RESULTS IN GREATER TENSION DEVELOPMENT IN PREVIOUSLY FATIGUED CANINE MUSCLE IN SITU
Richard A Howlett 1*,
Kevin M. Kelley 1,
Bruno Grassi 2,
L Bruce Gladden 3,
Michael C Hogan 1
1 University of California San Diego
2 Universita' degli Studi di Milano
3 Auburn University
* To whom correspondence should be addressed. E-mail: rhowlett{at}ucsd.edu.
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Abstract |
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In isolated single skeletal myocytes undergoing long-term fatiguing contractions, caffeine (CAF) can result in nearly immediate restoration of generated tension to near prefatigue levels by increasing Ca2+ release via activation of SR release channels. This study tested whether arterial CAF infusion (> [5mM]) would cause a similar rapid restoration of tetanic tension during contractions to fatigue in perfused canine hindlimb muscle in situ. Tetanic contractions were elicited by electrical stimulation (200ms trains, 50 Hz, 1 contraction/sec) and biopsies were taken from the muscle at rest and during contractions: 1) following the onset of fatigue (force ~ 60% of initial) and 2) following CAF administration. Resting muscle ATP, PCr, and lactate contents were 25.2 ± 0.4, 76.9 ± 3.3, and 14.4 ± 3.3 mmol/kg dry weight (dw), respectively. At fatigue, force of tetanic contractions was 61.1 ± 6.9 % of initial. There was a small but statistically significant recovery of tetanic force (64.9 ± 6.6 % initial) with CAF infusion followed by the muscle showing incomplete relaxation. At fatigue, muscle ATP and PCr contents had fallen significantly (p < 0.05) to 18.1 ± 1.1 and 18.9 ± 2.1 mmol/kg dw, respectively, and lactate content had increased significantly to 27.7 ± 5.4 mmol/kg dw. Following CAF, skeletal muscle ATP and PCr were significantly lower than fatigue values (15.0 ± 1.3 and 10.9 ± 2.2 mmol/kg dw, respectively), while lactate was unchanged (22.2 ± 3.9 mmol/kg dw). These results demonstrate that caffeine can result in a small, but statistically significant recovery of isometric tension in fatigued canine hindlimb muscle in situ, although not nearly to the same degree as seen in isolated single muscle fibers. This suggests that, in this in situ isolated whole muscle model, alteration of Ca2+ metabolism is likely only one cause of fatigue.
Key Words:
Calcium, Electrical stimulation, Sarcoplasmic reticulum
