title: Monophasic action potentials and Ca2+transients in ischaemically preconditioned rabbit ventricular muscle.
abstract: BACKGROUND
  ATP-sensitive K+(KATP) channels play an important role in the protective mechanism underlying ischaemic preconditioning. Ample evidence indicates, however, that action potential shortening is not a prerequisite for the cardioprotective effect of preconditioning.
  
  
  METHODS
  Monophasic action potential duration (MAPD), tissue resistance, intracellular Ca2+(Indo-1) and mechanical activity were simultaneously assessed in arterially perfused rabbit papillary muscles. We studied four experimental protocols preceding sustained ischaemia: 1. control perfusion (n=6), 2. ischaemic preconditioning (PC; n=4), 3. pretreatment with a KATPchannel blocker, glibenclamide (15 μmol/1), prior to ischaemic preconditioning (PC+glib; n=3), 4. glibenclamide pretreatment only (Glib; n=2).
  
  
  RESULTS
  In the PC group an increase in the diastolic Ca2+level and a prolongation of the Ca2+transient just prior to the induction of sustained ischaemia correlate to the postponement of the onset of irreversible ischaemic damage, as established by a rise in [Ca2+]i, electrical uncoupling and contracture. Glibenclamide antagonised these changes in the Ca2+transient and the cardioprotection induced by preconditioning. MAPD was equal in all experimental groups.
  
  
  CONCLUSIONS
  Prolongation of the Ca2+transient and increase of diastolic [Ca2+]ijust prior to the induction of sustained ischaemia and not action potential shortening are involved in the cardioprotective effect of ischaemic preconditioning. Therefore, a glibenclamide-sensitive mechanism, other than the sarcolemmal KATPchannels, is involved in the protective effect of ischaemic preconditioning. Changes in Ca2+metabolism may play a crucial role in ischaemic preconditioning.
authors.forename: L R C
authors.initials: LR
authors.lastname: Dekker
authors.forename: E
authors.initials: E
authors.lastname: van Bavel
authors.forename: T
authors.initials: T
authors.lastname: Opthof
authors.forename: R
authors.initials: R
authors.lastname: Coronel
authors.forename: M J
authors.initials: MJ
authors.lastname: Janse
keywords: ATP-sensitive K+ channels; Ca2+ transients; monophasic action potentials; preconditioning