Increase in number of myocardial [3H]BAY K 8644 binding sites during adult maturation of rat

Abstract

In the present study we investigated the binding properties of [3H]BAY K 8644 to the purified sarcolemmal membrane, isolated from 2- and 12-month old Sprague–Dawley rats. Specific binding of [3H]BAY K 8644 was saturable and the Scatchard plot analysis revealed a single class of binding sites in purified sarcolemmal membrane. The estimated maximum number of binding sites in the membrane of 12-month-old rat was 2.4 ± 0.1 pmol/mg protein, which was significantly greater than the maximum number of binding sites in 2-month-old rats (1.7 ± 0.2 pmol/mg protein). The affinity to bind [3H]BAY K 8644 was, however, reduced in older rats (KD, 14.5 ± 0.8 vs. 4.8 ± 0.3 nM). Measurement of activities of sarcolemmal and subcellular marker enzymes showed that the purification of membrane was virtually identical in two age groups. This would suggest that membrane purity was not a contributing factor to the observed increase in [3H]BAY K 8644 receptor density. Since dihydropyridine receptor sites are very likely to represent voltage-gated calcium channels of sarcolemma, it is concluded that the density of myocardial voltage-gated calcium channels increases during adult maturation.Key words: BAY K 8644, Ca2+ channel, maturation, age.