Role of diprotonated phosphate in evoking muscle reflex responses in cats and humans

L. I. Sinoway, M. B. Smith, B. Enders, U. Leuenberger, T. Dzwonczyk, K. Gray, S. Whisler, R. L. Moore

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Lactic acid and H+ evoke muscle reflexes that raise sympathetic nerve activity. Whether these substances are direct afferent stimulants or markers for the acidification of other substances is unknown. Diprotonated phosphate (H2PO4/-), a possible mediator of fatigue, increases as the cell acidifies and phosphate is produced. Its role in evoking muscle reflexes is unknown. We used 31P-nuclear magnetic resonance to measure forearm muscle H+ and H2PO4/- and microneurography to measure muscle sympathetic nerve activity (MSNA, peroneal nerve) during a handgrip protocol designed to dissociate H+ from H2PO4/-. Ischemic handgrip (50% maximal voluntary contraction x 2 min) was followed by a 1-min rest period during which the muscle was freely perfused. This was followed by a second bout of ischemic handgrip and a 5- min recovery. In seven of eight subjects, MSNA correlated with H2PO4/-, whereas it correlated with pH in only one subject. To determine whether muscle reflex responses are evoked by H+, lactic acid, monoprotonated phosphate (HPO4/2-), or H2PO4/-, we injected H+, lactate, H2PO4/- [all 50 mM in 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffered to pH 6], and HPO4/2- (50 mM, pH 7.5 in 10 mM HEPES) into the arterial supply of the triceps surae of the cat (n = 9) as we measured mean arterial blood pressure (MAP). H2PO4/- increased MAP more than HPO4/2-, H+, or lactate (27.1 ± 3.7 vs. 5.0 ± 1.3, 4.6 ± 3.1, and 7.7 ± 3.2 rise in mmHg). This effect was a reflex, since H2PO4/- did not raise MAP after the sciatic nerve was cut. Thus H2PO4/- is a major stimulant of muscle afferents and in large part determines the degree of sympathoexcitation during exercise.

Original languageEnglish (US)
Pages (from-to)H770-H778
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number2 36-2
StatePublished - 1994

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


Dive into the research topics of 'Role of diprotonated phosphate in evoking muscle reflex responses in cats and humans'. Together they form a unique fingerprint.

Cite this