Dietary nitrate increases tetanic [Ca2+]i and contractile force in mouse fast-twitch muscle.
Dietary inorganic nitrate has profound effects on health and physiological responses to exercise. Here, we examined if nitrate, in doses readily achievable via a normal diet, could improve Ca(2+) handling and contractile function using fast- and slow-twitch skeletal muscles from C57bl/6 male mice given 1 mm sodium nitrate in water for 7 days. Age matched controls were provided water without added nitrate. In fast-twitch muscle fibres dissected from nitrate treated mice, myoplasmic free [Ca(2+)] was significantly greater than in Control fibres at stimulation frequencies from 20 to 150 Hz, which resulted in a major increase in contractile force at ≤ 50 Hz. At 100 Hz stimulation, the rate of force development was ∼35% faster in the nitrate group. These changes in nitrate treated mice were accompanied by increased expression of the Ca(2+) handling proteins calsequestrin 1 and the dihydropyridine receptor. No changes in force or calsequestrin 1 and dihydropyridine receptor expression were measured in slow-twitch muscles. In conclusion, these results show a striking effect of nitrate supplementation on intracellular Ca(2+) handling in fast-twitch muscle resulting in increased force production. A new mechanism is revealed by which nitrate can exert effects on muscle function with applications to performance and a potential therapeutic role in conditions with muscle weakness.
Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. andres.hernandez@ki.se
Andrés
A
Hernández
Tomas A
TA
Schiffer
Niklas
N
Ivarsson
Arthur J
AJ
Cheng
Joseph D
JD
Bruton
Jon O
JO
Lundberg
Eddie
E
Weitzberg
Håkan
H
Westerblad
D000818:Animals; D002118:Calcium / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000502:physiology; D002155:Calsequestrin / Q000502:physiology; D004032:Diet; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects*; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects* / Q000502:physiology; D009566:Nitrates / Q000008:administration & dosage*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology
D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D002155:Calsequestrin; C503130:Casq1 protein, mouse; D009566:Nitrates; D019837:Ryanodine Receptor Calcium Release Channel; C514388:casq2 protein, mouse; D002118:Calcium