We previously found that a @entity235 model of selective surgical @entity67 ( @entity712 ), which does not permit increased sympathetic tone during the pathogenesis of @entity712 ( @entity712 ), tolerated the development of @entity712 better than controls. To investigate the cellular mechanisms, we examined cellular contraction and L-type @entity141 channel currents (I( @entity9495 )) and their responses to beta-adrenergic receptor (beta-AR) stimulation in left ventricular myocytes from 1) control, 2) @entity712 , 3) @entity712 induced by rapid pacing, and 4) @entity712 induced in @entity712 ( @entity712 ) @entity235 . The magnitude of myocyte contraction and rate of relaxation in @entity712 were similar to control but were @entity712 . These changes were associated with reduced protein expression of sarcoplasmic reticulum @entity141 -ATPase ( @entity16089 ) and protein kinase A phosphorylated phospholamban (PLB), which was reduced in @entity712 , but essentially abolished in @entity712 . beta-AR kinase (GRK2) was increased in @entity712 but reduced in @entity712 . Basal I( @entity9495 ) density did not differ among control, @entity712 , and @entity712 groups, but @entity712 myocytes showed a markedly reduced I( @entity9495 ) density (approximately 40%). Compared to controls, the sensitivity of I( @entity9495 ) to @entity3044 ( @entity8670 ), was significantly higher in @entity712 , but reduced in @entity712 . While I( @entity9495 ) responses to @entity8670 in @entity712 were maintained at control levels, the amplitude of the @entity8670 -stimulated I( @entity9495 ) was significantly smaller (approximately 50%) compared with @entity712 myocytes. The relative decrease in @entity141 influx due to downregulation of I( @entity9495 ) density may contribute to the cardioprotective effects in @entity712 hearts by preventing @entity141 overload during the development of @entity712 . These findings, in combination with the virtual abolition of phosphorylated PLB in @entity712 and the decrease in GRK2, may explain, in part, why @entity712 @entity235 tolerate the development of @entity712 better than control @entity235 .

Down regulation of the L-type XXXX channel, GRK2, and phosphorylated phospholamban: protective mechanisms for the denervated failing heart.

@entity712 :: ('MESH:D006333', 'Disease') :: ['HF', 'depressed in both HF and VD-HF', 'VD-HF', 'VD', 'heart failure'] @entity16089 :: ('403878(Tax:9615)', 'Gene') :: ['SERCA2a'] @entity235 :: ('9615', 'Species') :: ['canine', 'dogs'] @entity3044 :: ('MESH:D007545', 'Chemical') :: ['isoproterenol'] @entity8670 :: ('D007545', 'Chemical') :: ['ISO'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity67 :: ('MESH:D018754', 'Disease') :: ['ventricular denervation'] @entity9495 :: ('D002118', 'Chemical') :: ['Ca']
@entity141 :: (CHEBI:29108,Chemical) :: ['Ca2+']
