Coregulation of calcium channels and beta-adrenergic receptors in cultured chick embryo ventricular cells

Journal Article · Fri Sep 01 04:00:00 EDT 1989 · Journal of Clinical Investigation; (USA)

DOI:https://doi.org/10.1172/JCI114241· OSTI ID:5189590

Marsh, J D ^[1]

---

1. Brigham and Women's Hospital, Boston, MA (USA)

To examine mechanisms whereby the abundance of functional Ca channels may be regulated in excitable tissue, Ca channel number was estimated by binding of the dihydropyridine (DHP) antagonist {sup 3}H (+)PN200-110 to monolayers of intact myocytes from chick embryo ventricle. Beta adrenergic receptor properties were studied in cultured myocytes using ({sup 3}H)CGP12177, an antagonist ligand. Physiological correlates for alterations in DHP binding site number included {sup 45}Ca uptake and contractile response to (+)BAYk 8644, a specific L-type Ca channel activator. All binding and physiological determinations were performed in similar intact cell preparations under identical conditions. 4-h exposure to 1 microM isoproterenol reduced cell surface beta-adrenergic receptor number from 44 +/- 3 to 17 +/- 2 fmol/mg (P less than 0.05); DHP binding sites declined in number from 113 +/- 25 to 73 +/- 30 fmol/mg (P less than 0.03). When protein kinase A was activated by a non-receptor-dependent mechanism, DHP binding declined similarly to 68% of control. Exposure to diltiazem, a Ca channel antagonist, for 18-24 h had no effect on number of DHP binding sites. After 4-h isoproterenol exposure, {sup 45}Ca uptake stimulated by BAYk 8644 declined from 3.3 +/- 0.2 nmol/mg to 2.9 +/- 0.3 nmol/mg (P less than 0.01) and BAYk 8644-stimulated increase in amplitude of contraction declined from 168 +/- 7 to 134 +/- 11% (P = 0.02). Thus, elevation of (cAMP) in myocytes is associated with a time-dependent decline in Ca channel abundance as estimated by DHP binding and a decline in physiological responses that are in part dependent on abundance of Ca channels. Binding of a directly acting Ca channel antagonist for 18-24 h does not modulate the number of DHP binding sites.

• OSTI ID: 5189590
• Journal Information: Journal of Clinical Investigation; (USA), Journal Name: Journal of Clinical Investigation; (USA) Journal Issue: 3 Vol. 84:3; ISSN 0021-9738; ISSN JCINA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH ISOTOPES
AMINES
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CALCIUM 45
CALCIUM ISOTOPES
CARDIOVASCULAR SYSTEM
CELL CULTURES
CONTRACTION
DAYS LIVING RADIOISOTOPES
DRUGS
EMBRYOS
EVEN-ODD NUCLEI
HEART
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MEMBRANE PROTEINS
MUSCLES
MYOCARDIUM
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PORINS
PROTEINS
PYRIDINE
PYRIDINES
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
SYMPATHOMIMETICS
TIME DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS