We previously found that a canine model of selective surgical ventricular 
denervation (VD), which does not permit increased sympathetic tone during the 
pathogenesis of heart failure (HF), tolerated the development of HF better than 
controls. To investigate the cellular mechanisms, we examined cellular 
contraction and L-type Ca(2+) channel currents (I(Ca)) and their responses to 
beta-adrenergic receptor (beta-AR) stimulation in left ventricular myocytes from 
1) control, 2) VD, 3) HF induced by rapid pacing, and 4) HF induced in VD 
(VD-HF) dogs. The magnitude of myocyte contraction and rate of relaxation in VD 
were similar to control but were depressed in both HF and VD-HF. These changes 
were associated with reduced protein expression of sarcoplasmic reticulum 
Ca(2+)-ATPase (SERCA2a) and protein kinase A phosphorylated phospholamban (PLB), 
which was reduced in HF, but essentially abolished in VD-HF. beta-AR kinase 
(GRK2) was increased in HF but reduced in VD-HF. Basal I(Ca) density did not 
differ among control, VD, and HF groups, but VD-HF myocytes showed a markedly 
reduced I(Ca) density (approximately 40%). Compared to controls, the sensitivity 
of I(Ca) to isoproterenol (ISO), was significantly higher in VD, but reduced in 
HF. While I(Ca) responses to ISO in VD-HF were maintained at control levels, the 
amplitude of the ISO-stimulated I(Ca) was significantly smaller (approximately 
50%) compared with HF myocytes. The relative decrease in Ca(2+) influx due to 
downregulation of I(Ca) density may contribute to the cardioprotective effects 
in VD-HF hearts by preventing Ca(2+) overload during the development of HF. 
These findings, in combination with the virtual abolition of phosphorylated PLB 
in VD-HF and the decrease in GRK2, may explain, in part, why VD dogs tolerate 
the development of HF better than control dogs.