Calcium channel binding characteristics in the human heart.
The number, affinity, pharmacologic specificity and regional distribution of calcium channel binding sites in human hearts obtained at autopsy and open heart surgery were characterized using the radioligand [3H]nitrendipine. Scatchard analyses of saturation data from 6 autopsy hearts revealed a homogeneous distribution of high affinity binding sites (affinity-1 [KD] = 0.44 +/- 0.06, 0.52 +/- 0.07, 0.32 +/- 0.02, 0.30 +/- 0.03, and 0.45 +/- 0.01 nM; binding capacity [Bmax] = 30 +/- 4, 27 +/- 6, 25 +/- 7, 33 +/- 3, and 28 +/- 4 fmol/mg protein in right atrium, right ventricle, left atrium, left ventricle and ventricular septum, respectively). In ligand competition experiments, nifedipine and nitrendipine completely displaced binding with partial displacement by verapamil and 35% enhancement of binding by 10(-5) M diltiazem at 37 degrees. Analyses of right atrial appendages obtained at open heart surgery from 5 coronary artery bypass patients provided similar results (KD = 0.2 +/- 0.03 nM, Bmax = 42 +/- 2 fmol/mg protein). In addition, no significant differences in KD or Bmax were found in 3 hamster hearts assayed at the time of death or up to 18 hours postmortem at either 4 or 25 degrees. In contrast, there was a significant increase in Bmax (110 fmol/mg protein) with no change in KD (0.3 nM) in a myomectomy specimen from a patient with obstructive hypertrophic cardiomyopathy compared with either autopsy or surgical specimens. These studies illustrate the feasibility and potential advantages of studying calcium channels directly in human hearts.
Finkel
M S
MS
Department of Medicine, University of Pittsburgh, Pennsylvania 15213.
Patterson
R E
RE
Roberts
W C
WC
Smith
T D
TD
Keiser
H R
HR
D000328:Adult; D001665:Binding Sites / Q000187:drug effects; D015220:Calcium Channels / Q000378:metabolism*; D005260:Female; D006325:Heart Atria; D006352:Heart Ventricles; D006801:Humans; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure*; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism
D015220:Calcium Channels; D011956:Receptors, Cell Surface; D009568:Nitrendipine; D009543:Nifedipine