title: Influence of verapamil on tachycardia-induced alterations of PP1 and PP2A in rabbit atrium.
abstract: BACKGROUND
  Long-term atrial fibrillation changes in many regulatory and structural processes may result in stabilization of the arrhythmia. There is evidence that decreased amplitude of L-type Ca(2+) current - probably a key mechanism of atrial remodelling -resulting from changes in expression of regulatory proteins is at least jointly responsible.
  
  
  OBJECTIVE
  To assess the expressions of protein phosphatases PP1 and PP2A, as well as the effect of verapamil pretreatment (VPT), in the early phases of atrial fibrillation in a rabbit model.
  
  
  METHODS
  FOUR GROUPS, EACH CONSISTING OF SIX ANIMALS, WERE STUDIED: 'not paced, no drug' group; 'paced, no drug' group (rapid atrial pacing [RAP] 600 beats/min for 24 h); 'not paced, verapamil' (NPV) group (duration of VPT was seven days, verapamil 7.5 mg/kg was administered every 12 h); and 'paced, verapamil' (PV) group (pacemaker stimulation after VPT). Protein expression was evaluated by Western blot analysis.
  
  
  RESULTS
  RAP resulted in an augmented (32%) PP1 expression (not paced, no drug group versus paced, no drug group). The increase in PP1 expression was prevented with VPT (NPV group versus PV group). Expression of PP2A was not influenced by RAP. However, VPT led to an increase of PP2A expression (16%) after RAP (NPV group versus PV group).
  
  
  CONCLUSIONS
  Fortified expression of protein phosphatases might be - besides transcriptional downregulation of channel subunits - another important cause of reduced L-type Ca(2+) current after RAP. Blocking L-type Ca(2+) channels with verapamil to prevent tachycardia-induced changes of PP1 expression might be expedient.
authors.affiliation: Department of Cardiology;
authors.forename: Roman
authors.initials: R
authors.lastname: Laszlo
authors.forename: Christoph
authors.initials: C
authors.lastname: Winkler
authors.forename: Stefan
authors.initials: S
authors.lastname: Wöhrl
authors.forename: Sara
authors.initials: S
authors.lastname: Laszlo
authors.forename: Christian
authors.initials: C
authors.lastname: Eick
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schreieck
authors.forename: Ralph F
authors.initials: RF
authors.lastname: Bosch