Altered calcium (Ca2+) mobilization after burn trauma: Beneficial effects of calcium antagonist dantrolene

D. Maass, J. W. Horton, D. J. White, M. Thompson, B. Giroir, G. Arteaga

Research output: Contribution to journalArticlepeer-review

Abstract

Numerous studies have shown that elevated intracellular calcium concentration [Ca2+]i occurs in several cell types after stress related injury. However, the mechanism responsible for the increased [Ca2+]i (that is, altered Ca2+ release or uptake from intracellular organelles such as the sarcoplasmic reticulum, SR, versus altered Ca2+ influx) remains unclear. This study examined the contribution of SR dysfunction to postburn Ca2+ dyshomeostasis in burn injury. Rats were given a 3° burn over 43% TBSA and fluid treated for 24 hours (n=18); sham burns were included for controls (n=19). Hearts were harvested 24 hrs postburn and Ca2+ uptake was measured in myocardial homogenates and normalized for protein concentration. Compared to shams, maximal Ca2+ uptake capacity (350±10 nmoles/ng protein) and Ca2+ uptake velocity (58±2 nmole/mg/min) were reduced after burn trauma (292±15, p<0.01 and 49±1, p<0.01 respectively). In additional studies, burned rats (n=9) received dantrolene a drug which blocks Ca2+ release from the SR (10 mg/kg, IV, 30 min, 8 hrs, and 20 hrs postburn); shams received vehicle. Myocytes were isolated (collagenase digestion) 24 hrs postburn. Fura-2 loaded cells (1×105/ml) were excited at wavelengths of 340/380 nm (Hitachi spectrofluorometer) and [Ca2+]i was calculated from fura-2 ratios. Burn trauma increased myocyte [Ca2+]i compared to shams (152±6 vs 307±29 nm, p<0.05); dantrolene reduced the postburn rise in [Ca2+] , (164±22 nm, p<0.05). The ability of dantrolene to normalize myocyte [Ca2+]i coupled with abnormalities in SR Ca2+ transport suggest that postburn Ca2+ dyshomeostasis is related to the defects in up take/release of Ca2+ from the SR.

Original languageEnglish (US)
Pages (from-to)A286
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Altered calcium (Ca<sup>2+</sup>) mobilization after burn trauma: Beneficial effects of calcium antagonist dantrolene'. Together they form a unique fingerprint.

Cite this