β-Adrenergic activation reveals impaired cardiac calcium handling at early stage of diabetes

Jorn Op Den Buijs, Zsuzsanna Miklós, Natal A W Van Riel, Christina M. Prestia, Orsolya Szenczi, András Tóth, Ger J. Van Der Vusse, Csaba Szabo, László Ligeti, Tamás Ivanics

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Cardiac function is known to be impaired in diabetes. Alterations in intracellular calcium handling have been suggested to play a pivotal role. This study aimed to test the hypothesis that β-adrenergic activation can reveal the functional derangements of intracellular calcium handling of the 4-week diabetic heart. Langendorff perfused hearts of 4-week streptozotocin-induced diabetic rats were subjected to the β-adrenoceptor agonist isoproterenol. Cyclic changes in [Ca 2+] i levels were measured throughout the cardiac cycle using Indo-1 fluorescent dye. Based on the computational analysis of the [Ca 2+] i transient the kinetic parameters of the sarcoplasmic reticulum Ca 2+-ATPase and the ryanodine receptor were determined by minimizing the squared error between the simulated and the experimentally obtained [Ca 2+] i transient. Under unchallenged conditions, hemodynamic parameters were comparable between control and diabetic hearts. Isoproterenol administration stimulated hemodynamic function to a greater extent in control than in diabetic hearts, which was exemplified by more pronounced increases in rate of pressure development and decline. Under unchallenged conditions, [Ca 2+] i amplitude and rate of rise and decline of [Ca 2+] i as measured throughout the cardiac cycle were comparable between diabetic and control hearts. Differences became apparent under β-adrenoceptor stimulation. Upon β-activation the rate-pressure product showed a blunted response, which was accompanied by a diminished rise in [Ca 2+] i amplitude in diabetic hearts. Computational analysis revealed a reduced function of the sarcoplasmic reticulum Ca 2+-ATPase and Ca 2+-release channel in response to β-adrenoceptor challenge. Alterations in Ca 2+ i handling may play a causative role in depressed hemodynamic performance of the challenged heart at an early stage of diabetes.

Original languageEnglish (US)
Pages (from-to)1083-1098
Number of pages16
JournalLife Sciences
Volume76
Issue number10
DOIs
StatePublished - Jan 21 2005
Externally publishedYes

Fingerprint

Medical problems
Adrenergic Agents
Chemical activation
Calcium
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Hemodynamics
Adrenergic Receptors
Isoproterenol
Pressure
Ryanodine Receptor Calcium Release Channel
Streptozocin
Fluorescent Dyes
Kinetic parameters
Rats

Keywords

  • Calcium handling
  • Computational modeling
  • Diabetic cardiomyopathy

ASJC Scopus subject areas

  • Pharmacology

Cite this

Op Den Buijs, J., Miklós, Z., Van Riel, N. A. W., Prestia, C. M., Szenczi, O., Tóth, A., ... Ivanics, T. (2005). β-Adrenergic activation reveals impaired cardiac calcium handling at early stage of diabetes. Life Sciences, 76(10), 1083-1098. https://doi.org/10.1016/j.lfs.2004.08.018

β-Adrenergic activation reveals impaired cardiac calcium handling at early stage of diabetes. / Op Den Buijs, Jorn; Miklós, Zsuzsanna; Van Riel, Natal A W; Prestia, Christina M.; Szenczi, Orsolya; Tóth, András; Van Der Vusse, Ger J.; Szabo, Csaba; Ligeti, László; Ivanics, Tamás.

In: Life Sciences, Vol. 76, No. 10, 21.01.2005, p. 1083-1098.

Research output: Contribution to journalArticle

Op Den Buijs, J, Miklós, Z, Van Riel, NAW, Prestia, CM, Szenczi, O, Tóth, A, Van Der Vusse, GJ, Szabo, C, Ligeti, L & Ivanics, T 2005, 'β-Adrenergic activation reveals impaired cardiac calcium handling at early stage of diabetes', Life Sciences, vol. 76, no. 10, pp. 1083-1098. https://doi.org/10.1016/j.lfs.2004.08.018
Op Den Buijs J, Miklós Z, Van Riel NAW, Prestia CM, Szenczi O, Tóth A et al. β-Adrenergic activation reveals impaired cardiac calcium handling at early stage of diabetes. Life Sciences. 2005 Jan 21;76(10):1083-1098. https://doi.org/10.1016/j.lfs.2004.08.018
Op Den Buijs, Jorn ; Miklós, Zsuzsanna ; Van Riel, Natal A W ; Prestia, Christina M. ; Szenczi, Orsolya ; Tóth, András ; Van Der Vusse, Ger J. ; Szabo, Csaba ; Ligeti, László ; Ivanics, Tamás. / β-Adrenergic activation reveals impaired cardiac calcium handling at early stage of diabetes. In: Life Sciences. 2005 ; Vol. 76, No. 10. pp. 1083-1098.
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