Density of 1,4-dihydropyridine receptors decreases in the hearts of aging hamsters.
To determine whether density and properties of myocardial voltage-sensitive calcium channels may change in the hearts of aged animals, we have compared specific binding of [3H]-nitrendipine ([3H]-NTP) to 1,4-dihydropyridine (DHP) receptors in ventricular homogenate and membrane fractions prepared from the hearts of adult hamsters of different ages. In crude homogenate preparations from young adult animals (70 days) the density (Bmax) of [3H]-NTP binding was 82 +/- 6 fmol/mg protein (n = 5 hearts). By contrast, Bmax values for 400-, 500- and 600-day-old animals were 54 +/- 5, 59 +/- 11 and 50 +/- 2 fmol/mg protein, respectively (significantly lower than control, P = 0.004, n = 4-5 hearts/group). The affinity (Kd) of [3H]-NTP binding was not affected by increasing age. Similar results were obtained in a partially purified membrane fraction. Allosteric modulation of [3H]-NTP binding by the phenylalkylamine, verapamil and the benzothiazepine, diltiazem were preserved in aging heart. These studies demonstrate that the density of myocardial DHP receptors declines in the aged hamster, although the properties of these receptors are unchanged. This suggests that a decrease in voltage-sensitive calcium channels may be associated with normal myocardial aging.
Howlett
S E
SE
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Nicholl
P A
PA
D000375:Aging / Q000378:metabolism*; D000495:Allosteric Site; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D004095:Dihydropyridines / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D004095:Dihydropyridines; C038806:1,4-dihydropyridine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine