title: Soluble substances released from postischemic reperfused rat hearts reduce calcium transient and contractility by blocking the L-type calcium channel.
abstract: OBJECTIVE
  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.
authors.affiliation: Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität Greifswald, Germany. felix@mail.uni-greifswald.de
authors.forename: S B
authors.initials: SB
authors.lastname: Felix
authors.forename: V
authors.initials: V
authors.lastname: Stangl
authors.forename: P
authors.initials: P
authors.lastname: Pietsch
authors.forename: P
authors.initials: P
authors.lastname: Bramlage
authors.forename: A
authors.initials: A
authors.lastname: Staudt
authors.forename: S
authors.initials: S
authors.lastname: Bartel
authors.forename: E G
authors.initials: EG
authors.lastname: Krause
authors.forename: J U
authors.initials: JU
authors.lastname: Borschke
authors.forename: K D
authors.initials: KD
authors.lastname: Wernecke
authors.forename: G
authors.initials: G
authors.lastname: Isenberg
authors.forename: G
authors.initials: G
authors.lastname: Baumann
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000502:physiology*; D009201:Myocardial Depressant Factor / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D006005:Phosphorylases / Q000037:antagonists & inhibitors; D051381:Rats
chemical_list: D020746:Calcium Channels, L-Type; D009201:Myocardial Depressant Factor; D006005:Phosphorylases; D002118:Calcium