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

Item Type:Article
Title:Soluble substances released from postischemic reperfused rat hearts reduce calcium transient and contractility by blocking the L-type calcium channel
Creators Name:Felix, S.B. and Stangl, V. and Pietsch, P. and Bramlage, P. and Staudt, A. and Bartel, S. and Krause, E.G. and Borschke, J.U. and Wernecke, K.D. and Isenberg, G. and Baumann, G.
Abstract: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, Ca 2+ transients and Ca 2+ 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 Ca 2+ transient in the field-stimulated isolated cardiomyocytes of rats, as well as a reduction in peak L-type Ca 2+ 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 Ca 2+ 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 Ca 2+ transient and cell contraction through cAMP-independent and cGMP-independent blockage of L-type Ca 2+ channels.
Keywords:Calcium, L-Type Calcium Channels, Myocardial Contraction, Myocardial Depressant Factor, Myocardial Reperfusion Injury, Phosphorylases, Animals, Rats
Source:Journal of the American College of Cardiology
Page Range:668-675
Date:1 January 2001
Official Publication:https://doi.org/10.1016/S0735-1097(00)01132-3
PubMed:View item in PubMed

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