Developmental regulation of cardiac calcium channels and contractile sensitivity to [Ca]o.
To test the hypothesis that alterations in Ca-channel properties are a major factor in developmental changes in Ca sensitivity of the heart, we quantitated Ca-channel pharmacological properties during development of the chick heart and related pharmacological properties of Ca channels to the ability of channels to modulate contractility. Force-pCa curves were determined for chick hearts during development. From 3 to 5 days in ovo to 3-4 days posthatched, there was more than 1 log decrease in sensitivity to extracellular calcium concentration [( Ca]o) PN200-100 ligand-binding studies in cardiac membranes revealed no change in dissociation constant (KD; 660-1,040 pM; P = NS) during development, but between 18 days in ovo and 3-4 days posthatched, there was an increase in the number of binding sites from 2,180 +/- 260 to 3,530 +/- 410 fmol/mg (P less than 0.01). This change could not be attributed to nonspecific change in membrane composition. For intact ventricular strips, there was a developmental decrease in contractile sensitivity to the Ca-channel agonist BAY K 8644 despite the increase in Ca channels as identified by ligand binding. Thus abundance of dihydropyridine binding sites increases during chick ventricular development, but this is dissociated from the physiological response to a Ca-channel agonist.
Marsh
J D
JD
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Allen
P D
PD
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D015220:Calcium Channels / Q000502:physiology*; D002642:Chick Embryo; D017275:Isradipine; D007700:Kinetics; D009200:Myocardial Contraction; D010069:Oxadiazoles / Q000494:pharmacology
D015220:Calcium Channels; D010069:Oxadiazoles; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D017275:Isradipine