Inhibition of creatine kinase reduces the rate of fatigue-induced decrease in tetanic [Ca2+]i in mouse skeletal muscle
Article first published online: 5 AUG 2004
The Journal of Physiology
Volume 533, Issue 3, pages 639–649, June 2001
How to Cite
Dahlstedt, A. J. and Westerblad, H. (2001), Inhibition of creatine kinase reduces the rate of fatigue-induced decrease in tetanic [Ca2+]i in mouse skeletal muscle. The Journal of Physiology, 533: 639–649. doi: 10.1111/j.1469-7793.2001.00639.x
- Issue published online: 5 AUG 2004
- Article first published online: 5 AUG 2004
- (Received 14 December 2000; accepted after revision 7 February 2001)
- 1Ca2+-phosphate (Pi) precipitation in the sarcoplasmic reticulum (SR) may cause reduced SR Ca2+ release in skeletal muscle fatigue. To study this, we inhibited the creatine kinase (CK) reaction with 2,4-dinitro-1-fluorobenzene (DNFB). The hypothesis was that with inhibition of CK, phosphocreatine would not break down to creatine and Pi. Therefore Pi transport into the SR would be limited and Ca2+-Pi precipitation would not occur.
- 2Intact single fibres from a mouse foot muscle were fatigued by repeated short tetani under control conditions or after exposure to DNFB (10 μM). The free myoplasmic concentrations of Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were measured with indo-1 and mag-indo-1, respectively. Changes in [Mg2+]i were assumed to reflect alterations in myoplasmic ATP concentration.
- 3During the first 10 fatiguing tetani, tetanic [Ca2+]i increased both in control and after DNFB exposure. Thereafter tetanic [Ca2+]i fell and the rate of fall was about fourfold lower after DNFB exposure compared with control.
- 4Under control conditions, there was a good relationship between declining tetanic [Ca2+]i and increasing [Mg2+]i during the final part of fatiguing stimulation. This correlation was lost after DNFB exposure.
- 5In conclusion, the present data fit with a model where Ca2+-Pi precipitation inhibits SR Ca2+ release in fatigue produced by repeated short tetani. Furthermore, the results suggest that the rate of Pi transport into the SR critically depends on the myoplasmic Mg2+/ATP concentration.