AJP - Heart and Circulatory Physiology, Vol 256, Issue 1 179-H185, Copyright © 1989 by American Physiological Society
Developmental regulation of cardiac calcium channels and contractile sensitivity to [Ca]o
J. D. Marsh and P. D. Allen
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
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.
