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Developmental regulation of cardiac calcium channels and contractile sensitivity to [Ca]o

J D Marsh1, P D Allen

  • 1Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.

The American Journal of Physiology
|January 1, 1989
PubMed

Insights

Cardiac development in chicks shows increased calcium channel numbers but decreased sensitivity to calcium channel agonists. This suggests developmental changes in calcium channel function, not just quantity, impact heart contractility.

Area of Science:

  • Cardiology
  • Developmental Biology
  • Pharmacology

Background:

  • Cardiac contractility is regulated by calcium (Ca) channels.
  • Developmental changes in the heart involve alterations in Ca sensitivity.
  • The precise role of Ca-channel properties in these developmental changes requires investigation.

Purpose of the Study:

  • To investigate the hypothesis that altered Ca-channel properties are key to developmental changes in cardiac Ca sensitivity.
  • To quantify Ca-channel pharmacological properties during chick heart development.
  • To correlate Ca-channel properties with their ability to modulate cardiac contractility.

Main Methods:

  • Determination of force-pCa curves in developing chick hearts.
  • Ligand-binding studies (PN200-100) on cardiac membranes to quantify Ca channels.
  • Assessment of contractile response to the Ca-channel agonist BAY K 8644 in ventricular strips.

Main Results:

  • Chick heart sensitivity to extracellular calcium concentration decreased by over 1 log during development.
  • The number of dihydropyridine binding sites (a measure of Ca channels) increased significantly from 18 days in ovo to posthatching.
  • Contractile sensitivity to the Ca-channel agonist BAY K 8644 decreased developmentally, despite the increase in Ca channels.

Conclusions:

  • Chick ventricular development involves an increase in the abundance of dihydropyridine binding sites.
  • This increase in Ca channels is dissociated from the physiological response to Ca-channel agonists.
  • Developmental changes in cardiac Ca sensitivity are not solely explained by alterations in Ca-channel quantity.

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