Dietary Nitrate Increases Tetanic [Ca2+]i and Contractile Force in Mouse Fast-Twitch Muscle

J Physiol. 2012 Aug 1;590(15):3575-83. doi: 10.1113/jphysiol.2012.232777. Epub 2012 Jun 11.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / physiology*
  • Calcium Channels, L-Type / physiology
  • Calcium-Binding Proteins / physiology
  • Calsequestrin / physiology
  • Diet
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Contraction / drug effects*
  • Muscle Fibers, Fast-Twitch / drug effects*
  • Muscle Fibers, Fast-Twitch / physiology
  • Nitrates / administration & dosage*
  • Ryanodine Receptor Calcium Release Channel / physiology

Substances

  • Calcium Channels, L-Type
  • Calcium-Binding Proteins
  • Calsequestrin
  • Casq1 protein, mouse
  • Nitrates
  • Ryanodine Receptor Calcium Release Channel
  • casq2 protein, mouse
  • Calcium