Developmental changes in the electrophysiological properties and the beta-adrenergic receptor-effector complex in atrial fibers of the canine coronary sinus.
beta-Adrenergic stimulation induced delayed afterdepolarizations and triggered activity in atrial fibers of adult but not young canine coronary sinus. However, sensitivity to beta-adrenergic agonists with respect to maximum diastolic potential was identical at both ages, and delayed afterdepolarizations and triggered activity did occur in response to ouabain. Age-dependent lengthening of the action potential duration and plateau also were seen and were greater in the adult than the young. beta-Adrenergic receptor density and affinity and the stimulatory guanine nucleotide regulatory protein (Gs) were similar in adult and young tissues. In contrast, the inhibitory guanine nucleotide regulatory protein (Gi) was 2.5-fold greater in adult (15 fmol/mg) than in young (6.0 fmol/mg) tissues. Basal- and forskolin-stimulated adenylate cyclase activities were greater in adult than young coronary sinus although the increment in isoproterenol-stimulated adenylate cyclase activity in young tissue was greater when compared either with basal levels or expressed as a percentage of maximal catalytic activity. Both the traditional effector pathway of beta-adrenergic action, involving the stimulation of adenylate cyclase activity, and developmental changes in the action potential plateau may contribute to the developmental changes in delayed afterdepolarizations and triggered activity.
Horn
E M
EM
Department of Pharmacology, Columbia University, New York, NY 10032.
Johnson
N J
NJ
Bilezikian
J P
JP
Rosen
M R
MR
D000200:Action Potentials; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002395:Catecholamines / Q000494:pharmacology; D004285:Dogs; D019204:GTP-Binding Proteins / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D006325:Heart Atria; D009206:Myocardium / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D010042:Ouabain; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases