This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Felix, S. B. Articles by Baumann, G. Search for Related Content PubMed PubMed Citation Articles by Felix, S. B. Articles by Baumann, G.

EXPERIMENTAL STUDY

Soluble substances released from postischemic reperfused rat hearts reduce calcium transient and contractility by blocking the L-type calcium channel

Stephan B. Felix, MD^*, Verena Stangl, MD, Peter Pietsch, PhD, Peter Bramlage, MD, Alexander Staudt, MD^*, Sabine Bartel, PhD, Ernst-Georg Krause, MD, J.örn-Uwe Borschke, MD, Klaus-Dieter Wernecke, PhD^||, Gerrit Isenberg, MD and Gert Baumann, MD

^* Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany
Medizinische Klinik und Poliklinik Charité, Kardiologie, Campus Mitte, Humboldt-Universität zu Berlin, Berlin, Germany
Max Delbrück Zentrum für molekulare Medizin, Berlin-Buch, Germany
Institut für Physiologie, Universität Halle, Halle, Germany
^|| Institut für Medizinische Biometrie, Charité, Humboldt-Universtät zu Berlin, Berlin, Germany

Manuscript received December 6, 1999; revised manuscript received August 22, 2000, accepted October 2, 2000.

Reprint requests and correspondence: Dr. Stephan Felix, Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität Greifswald, Friedrich Loeffler Strasse 23a, 17489 Greifswald, Germany
felix{at}mail.uni-greifswald.de

OBJECTIVES

This study was designed to investigate the effects of cardiodepressant substances released from postischemic myocardial tissue on myocardial calcium-regulating pathways.

BACKGROUND

We have recently reported that new cardiodepressant substances are released from isolated hearts during reperfusion after myocardial ischemia.

METHODS

After 10 min of global ischemia, isolated rat hearts were reperfused, and the coronary effluent was collected for 30 s. We tested the effects of the postischemic coronary effluent on cell contraction, Ca²⁺ transients and Ca²⁺ currents of isolated rat cardiomyocytes by applying fluorescence microscopy and the whole-cell, voltage-clamp technique. Changes in intracellular phosphorylation mechanisms were studied by measuring tissue concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), as well as activities of cAMP-dependent protein kinase (cAMP-dPK) and protein kinase C (PKC).

RESULTS

The postischemic coronary effluent, diluted with experimental buffer, caused a concentration-dependent reduction of cell shortening and Ca²⁺ transient in the field-stimulated isolated cardiomyocytes of rats, as well as a reduction in peak L-type Ca²⁺ current in voltage-clamped cardiomyocytes. The current reduction resulted from reduced maximal conductance—not from changes in voltage- and time-dependent gating of the L-type Ca²⁺ channel. The postischemic coronary effluent modified neither the tissue concentrations of cAMP or cGMP nor the activities of cAMP-dPK and PKC. However, the effluent completely eliminated the activation of glycogen phosphorylase after beta-adrenergic stimulation.

CONCLUSIONS

Negative inotropic substances released from isolated postischemic hearts reduce Ca²⁺ transient and cell contraction through cAMP-independent and cGMP-independent blockage of L-type Ca²⁺ channels.

Abbreviations and Acronyms   BSA = bovine serum albumin   cAMP = cyclic adenosine monophosphate   cAMP-d PK = cAMP-dependent protein kinase   cGMP = cyclic guanosine monophosphate   DMSO = dimethyl sulfoxide   KHB = Krebs-Henseleit buffer   NIS = negative inotropic substances   pA = picoampere   pF = picofarad   PKC = protein kinase C   pS = picosiemeus   rfu = relative fluorescence units   SR = sarcoplasmic reticulum

This article has been cited by other articles:

				S. Bien, A. Riad, C. A. Ritter, M. Gratz, F. Olshausen, D. Westermann, M. Grube, T. Krieg, S. Ciecholewski, S. B. Felix, et al. The Endothelin Receptor Blocker Bosentan Inhibits Doxorubicin-Induced Cardiomyopathy Cancer Res., November 1, 2007; 67(21): 10428 - 10435. [Abstract] [Full Text] [PDF]

				K. Birkenmeier, A. Staudt, W.-H. Schunck, I. Janke, C. Labitzke, T. Prange, C. Trimpert, T. Krieg, M. Landsberger, V. Stangl, et al. COX-2-dependent and potentially cardioprotective effects of negative inotropic substances released after ischemia Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2148 - H2154. [Abstract] [Full Text] [PDF]

				S. B. Felix, A. Staudt, M. Landsberger, Y. Grosse, V. Stangl, T. Spielhagen, G. Wallukat, K. D. Wernecke, G. Baumann, and K. Stangl Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption J. Am. Coll. Cardiol., February 20, 2002; 39(4): 646 - 652. [Abstract] [Full Text] [PDF]

				V. Stangl, G. Baumann, K. Stangl, and S. B Felix Negative inotropic mediators released from the heart after myocardial ischaemia-reperfusion Cardiovasc Res, January 1, 2002; 53(1): 12 - 30. [Abstract] [Full Text] [PDF]