High-frequency fatigue of skeletal muscle: role of extracellular Ca(2+).
The present study evaluated whether Ca(2+) entry operates during fatigue of skeletal muscle. The involvement of different skeletal muscle membrane calcium channels and of the Na(+)/Ca(2+) exchanger (NCX) has been examined. The decline of force was analysed in vitro in mouse soleus and EDL muscles submitted to 60 and 110 Hz continuous stimulation, respectively. Stimulation with this high-frequency fatigue (HFF) protocol, in Ca(2+)-free conditions, caused in soleus muscle a dramatic increase of fatigue, while in the presence of high Ca(2+) fatigue was reduced. In EDL muscle, HFF was not affected by external Ca(2+) levels either way, suggesting that external Ca(2+) plays a general protective role only in soleus. Calciseptine, a specific antagonist of the cardiac isoform (alpha1C) of the dihydropyridine receptor, gadolinium, a blocker of both stretch-activated and store-operated Ca(2+) channels, as well as inhibitors of P2X receptors did not affect the development of HFF. Conversely, the Ca(2+) ionophore A23187 increased the protective action of extracellular Ca(2+). KB-R7943, a selective inhibitor of the reverse mode of NCX, produced an effect similar to that of Ca(2+)-free solution. These results indicate that a transmembrane Ca(2+) influx, mainly through NCX, may play a protective role during HFF development in soleus muscle.
Germinario
Elena
E
Department of Human Anatomy and Physiology, University of Padova, Via Marzolo 3, 35131 Padova, Italy.
Esposito
Alessandra
A
Midrio
Menotti
M
Peron
Samantha
S
Palade
Philip T
PT
Betto
Romeo
R
Danieli-Betto
Daniela
D
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004546:Elapid Venoms / Q000494:pharmacology; D004558:Electric Stimulation; D045604:Extracellular Fluid / Q000378:metabolism*; D005682:Gadolinium / Q000494:pharmacology; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D018763:Muscle Fatigue / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004546:Elapid Venoms; D007476:Ionophores; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D019831:Sodium-Calcium Exchanger; D014227:Triazines; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D000001:Calcimycin; C067971:calciseptine; C012842:Cibacron Blue F 3GA; D011732:Pyridoxal Phosphate; D013498:Suramin; D005682:Gadolinium; D013890:Thiourea; D002118:Calcium