Cocaine downregulates cardiac SERCA2a and depresses myocardial function in the murine model.
Cocaine has been shown to depress myocardial function, which may be linked to abnormal Ca2+ handling by the sarcoplasmic reticulum (SR). To examine whether cocaine affects Ca(2+)-handling proteins and myocardial performance, we injected BALB/c mice with cocaine daily (30 mg/kg, i.p.) for 14 d. Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) levels, phospholamban (PLB) protein levels, and hemodynamic parameters were measured. After cocaine exposure, myocardial function was significantly decreased both in vivo and in vitro. Also, SERCA2a protein levels were significantly decreased in all cocaine-treated hearts (p < 0.05 compared with saline control). Normalized SERCA2a levels were 1.2 +/- 0.2 (densitometric units) in the cocaine groups (p < 0.05 compared with saline control). However, there was no statistical difference in PLB protein levels between the cocaine and the saline groups. In isolated papillary muscle studies, cocaine did not block the response to extracellular Ca2+ but it did prolong the relaxation time of the muscle. These results indicate that cocaine does not block extracellular Ca2+ entrance across the cell membrane, but that it decreases SERCA2a protein levels. In conclusion, our study demonstrates that cocaine decreases SERCA2a protein levels and depresses myocardial function.
Wang
Ju-Feng
JF
Yan
Xinhua
X
Min
Jiangyong
J
Sullivan
Matthew F
MF
Hampton
Thomas G
TG
Morgan
James P
JP
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D015536:Down-Regulation; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D016277:Ventricular Function, Left / Q000187:drug effects*; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D003042:Cocaine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban