Overexpression of the Na(+)-Ca2+ exchanger leads to enhanced inotropic responsiveness to Na(+)-channel agonist without sarcoplasmic reticulum protein changes in transgenic mice.
The present study investigated the influence of over-expression of the cardiac Na(+)-Ca2+ exchanger on myocardial force of contraction and alterations in sarcoplasmic reticulum (SR) Ca(2+)-handling proteins in a transgenic mouse model. Inotropic effects of Na+ channel agonist BDF 9148 and isoprenaline were determined in isolated electrically driven atria. Protein levels of key SR Ca(2+)-handling proteins were determined by Western blot analysis. Transgenic animals had no myocardial hypertrophy or failure. The positive inotropic effect of BDF 9148 was significantly more pronounced in myocardium for transgenic animals, whereas the inotropic response to isoprenaline was similar in both groups. Strong immunoreactivity of the transgene Na(+)-Ca2+ exchanger was detected in myocardium of transgenic animals. Protein levels of SR Ca(2+)-ATPase, phospholamban, and calsequestrin were unchanged. In conclusion, transgenic overexpression of the Na(+)-Ca2+ exchanger is accompanied by increased force development following Na+ channel agonist administration, even though Ca2+ proteins of the SR are unchanged.
Bäumer
A T
AT
Klinik III für Innere Medizin, Universität zu Köln, Germany.
Flesch
M
M
Kilter
H
H
Philipson
K D
KD
Böhm
M
M
D000818:Animals; D001384:Azetidines / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002155:Calsequestrin / Q000378:metabolism; D004285:Dogs; D015870:Gene Expression; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D062687:Sodium Channel Agonists; D019831:Sodium-Calcium Exchanger / Q000235:genetics* / Q000378:metabolism*; D000099211:Phospholamban
D001384:Azetidines; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002155:Calsequestrin; D007545:Isoproterenol; D011506:Proteins; D062687:Sodium Channel Agonists; D019831:Sodium-Calcium Exchanger; D000099211:Phospholamban; C071117:BDF 9148