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. OBJECTIVES: 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.
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. OBJECTIVES: 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: E G Daoud; B P Knight; R Weiss; M Bahu; W Paladino; R Goyal; K C Man; S A Strickberger; F Morady Journal: Circulation Date: 1997-09-02 Impact factor: 29.690
Authors: B J Brundel; I C van Gelder; R H Henning; A E Tuinenburg; L E Deelman; R G Tieleman; J G Grandjean; W H van Gilst; H J Crijns Journal: Cardiovasc Res Date: 1999-05 Impact factor: 10.787
Authors: I C Van Gelder; B J Brundel; R H Henning; A E Tuinenburg; R G Tieleman; L Deelman; J G Grandjean; P J De Kam; W H Van Gilst; H J Crijns Journal: J Cardiovasc Electrophysiol Date: 1999-04
Authors: L P Lai; M J Su; J L Lin; F Y Lin; C H Tsai; Y S Chen; S K Huang; Y Z Tseng; W P Lien Journal: J Am Coll Cardiol Date: 1999-04 Impact factor: 24.094
Authors: R G Tieleman; I C Van Gelder; H J Crijns; P J De Kam; M P Van Den Berg; J Haaksma; H J Van Der Woude; M A Allessie Journal: J Am Coll Cardiol Date: 1998-01 Impact factor: 24.094