Targeted inactivation of Galpha(i) does not alter cardiac function or beta-adrenergic sensitivity.
Inhibitory Galpha(i) protein increases in the myocardium during hypertrophy and has been associated with beta-adrenergic receptor (beta-AR) desensitization, contractile dysfunction, and progression of cardiac disease. The role of Galpha(i) proteins in mediating basal cardiac function and beta-AR response in nonpathological myocardium, however, is uncertain. Transgenic mice with targeted inactivation of Galpha(i2) or Galpha(i3) were examined for in vivo cardiac function with the use of conscious echocardiography and for ex vivo cardiac response to inotropic stimulation with the use of Langendorff blood-perfused isolated hearts and adult ventricular cardiomyocytes. Echocardiography revealed that percent fractional shortening and heart rate were similar among wild-type, Galpha(i2)-null, and Galpha(i3)-null mice. Comparable baseline diastolic and contractile performance was also observed in isolated hearts and isolated ventricular myocytes from wild-type mice and mice lacking Galpha(i) proteins. Isoproterenol infusion enhanced diastolic and contractile performance to a similar degree in wild-type, Galpha(i2)-null, and Galpha(i3)-null mice. These data demonstrate no observable role for inhibitory G proteins in mediating basal cardiac function or sensitivity to beta-AR stimulation in nonpathological myocardium.
Jain
M
M
Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02115, USA.
Lim
C C
CC
Nagata
K
K
Davis
V M
VM
Milstone
D S
DS
Liao
R
R
Mortensen
R M
RM
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D004452:Echocardiography; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D018095:Germ-Line Mutation; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D016296:Mutagenesis; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D007545:Isoproterenol