The force-frequency relationship is dependent on Ca(2+)-influx via L-type- and SR-Ca(2+)-channels in human heart

H Reuter, C Zobel, K Brixius, B Bölck, R H Schwinger

Publication: Contribution to journalJournal articlesResearchpeer-review

Abstract

UNLABELLED: The present study investigated the influence of Bay K 8644 and nifedipine (Nif) on the force-frequency relationship and on tetanic tension and force of contraction of failing human myocardium (PAP, n = 12). In addition, ryanodine (Rya) was studied on the force-frequency relationship. Bay K 8644 (0.1 microM) increased, but Nif (0.01 microM) reduced isometric force of contraction significantly. However, both, Bay K 8644 (2 Hz vs. 0.5 Hz:

CONTROL: -31.6 +/- 7.8%; +Bay K 8644: +103 +/- 30% (% basal); p < 0.005) as well as Nif (2 Hz vs. 0.5 Hz:

CONTROL: -8.8 +/- 9.7%; +Nif: +90.9 +/- 31.5% (% basal); p < 0.05), were able to restore a positive FFR in PAP. By measurement of tetanic tension and posttetanic potentiation in the presence of the 1,4-dihydropyridines, we support the hypothesis of the existence and functional relevance of a dihydropyridin-ryanodine receptor junctional complex. In skinned fiber preparations, Bay K 8644 showed no effect on Ca(2+)-sensitivity or caffeine induced Ca(2+)-release. Rya (10 microM) decreased force of contraction in PAP and was effective in restoring a positive FFR (2 Hz vs. 0.5 Hz:

CONTROL: -7.3 +/- 5.1%; +Rya: +98.0 +/- 31.9% (% basal); p < 0.05). Thus, the altered FFR and Ca(2+)-homeostasis in failing human myocardium may result from changes in sarcolemmal Ca(2+)-influx and/or from altered SR-Ca(2+)-load.

Original languageEnglish
JournalBasic research in cardiology
Volume94
Issue number3
Pages (from-to)159-70
Number of pages12
ISSN0300-8428
Publication statusPublished - 01.06.1999

Research areas and keywords

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Adult
  • Aged
  • Calcium
  • Calcium Channel Agonists
  • Calcium Channel Blockers
  • Calcium Channels
  • Heart Ventricles
  • Humans
  • Ion Transport
  • Middle Aged
  • Myocardial Contraction
  • Nifedipine
  • Sarcoplasmic Reticulum
  • Ventricular Function

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