Reduction of [Ca(2+)](i) restores uncoupled beta-adrenergic signaling in isolated perfused transgenic mouse hearts.
The effects of alterations in calcium in the perfusion media were studied on ss-adrenergic coupling in isolated hearts from 3 different transgenic mice: cardiac-specific overexpressed alpha(1) subunit of L-type calcium channel, overexpressed Galpha(q), and phospholamban knockout. Isolated hearts from all 3 models, when studied at [Ca(2+)] of 2 mmol/L in the perfusate, showed the usual blunted or no response to ss-adrenergic stimulation. Lowering [Ca(2+)] to 0.75 to 1.5 mmol/L unloaded the hearts of calcium and restored to nearly normal the responsiveness to ss-agonist stimulation.
Serikov
V B
VB
Institute of Molecular Pharmacology and Biophysics, Division of Cardiovascular Medicine, Department of Internal Medicine, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA.
Petrashevskaya
N N
NN
Canning
A M
AM
Schwartz
A
A
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000187:drug effects; D010641:Phenotype; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D000099211:Phospholamban
D002118:Calcium; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins; D007545:Isoproterenol; D011943:Receptors, Adrenergic, beta; D000099211:Phospholamban