Abstract |
Previous studies on single fast-twitch fibres from mouse toe muscles have shown marked fatigue-induced changes in the free myoplasmic [Ca2+] ([Ca2+]i), while mitochondrial [Ca2+] remained unchanged. We have now investigated whether muscle fibres from the legs of mice respond in a similar way. Intact, single fibres were dissected from the soleus and extensor digitorum longus (EDL) muscles of adult mice. To measure [Ca2+]i, indo-1 was injected into the isolated fibres. Mitochondrial [Ca2+] was measured using Rhod-2 and confocal laser microscopy. Fatigue was induced by up to 1000 tetanic contractions (70 Hz) given at 2 s intervals. In soleus fibres, there was no significant decrease in tetanic [Ca2+]i at the end of the fatiguing stimulation, whereas tetanic force was significantly reduced by about 30 %. In 10 out of 14 soleus fibres loaded with Rhod-2 and subjected to fatigue, mitochondrial [Ca2+] increased to a maximum after about 50 tetani; this increase was fully reversed within 20 min after the end of stimulation. The force-frequency curve of the non-responding soleus fibres was shifted to higher frequencies compared to that of the responding fibres. In addition, eight out of nine Rhod-2-loaded EDL fibres showed similar changes in mitochondrial [Ca2+] during and after a period of fatiguing stimulation. The stimulation-induced increase in mitochondrial [Ca2+] was reduced when mitochondria were depolarised by application of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, whereas it was increased by application of an inhibitor of the mitochondrial Na+/Ca2+ exchange (CGP-37157). In conclusion, isolated slow-twitch muscle fibres show only modest changes in tetanic force and [Ca2+]i during repeated contractions. The increase in mitochondrial Ca2+ does not appear to be essential for activation of mitochondrial ATP production, nor does it cause muscle damage.
|
Authors | Joseph Bruton, Pasi Tavi, Jan Aydin, Håkan Westerblad, Jan Lännergren |
Journal | The Journal of physiology
(J Physiol)
Vol. 551
Issue Pt 1
Pg. 179-90
(Aug 15 2003)
ISSN: 0022-3751 [Print] England |
PMID | 12815178
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Fluorescent Dyes
- Heterocyclic Compounds, 3-Ring
- Ionophores
- Thiazepines
- rhod-2
- Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
- Clonazepam
- CGP 37157
- Calcium
|
Topics |
- Animals
- Calcium
(metabolism)
- Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
(pharmacology)
- Clonazepam
(analogs & derivatives, pharmacology)
- Electric Stimulation
- Extremities
- Fluorescent Dyes
- Heterocyclic Compounds, 3-Ring
- Intracellular Membranes
(metabolism)
- Ionophores
(pharmacology)
- Male
- Mice
- Mice, Inbred Strains
- Microscopy, Confocal
- Mitochondria, Muscle
(metabolism)
- Muscle Contraction
(physiology)
- Muscle Fatigue
(physiology)
- Muscle Fibers, Slow-Twitch
(metabolism)
- Muscle, Skeletal
(metabolism, physiology)
- Osmolar Concentration
- Thiazepines
(pharmacology)
|