The binding of (+)-isradipine by guinea-pig intact atria.

1. The accumulation of [3H]-(+)-isradipine (PN 200-110) was measured in quiescent guinea-pig left atria with normal (K+ 2.7 mM) or lowered (K+ 40 mM) membrane potential. 2. Under control conditions (2.7 mM K+) a high affinity binding of (+)-isradipine could not be detected. If, however, the atria were partially depolarized to about -30 mV by 40 mM K+, high affinity binding became evident displaying a dissociation constant of 4.2 x 10(-11) M and a capacity of 9.7 nmol kg-1 wet wt. 3. The depolarization-induced binding was reversible upon repolarization of the atria although isradipine was still present in the medium. This indicates that the high affinity binding sites disappear as soon as the cell membranes become polarized. 4. Isradipine belongs to the less hydrophobic dihydropyridines, but nevertheless the unsaturable binding led to an accumulation of about 84 fold. At a concentration of 2 x 10(-8) M (+)-isradipine, which reduces the contractile force by 50%, the cellular concentration will rise to more than 10(-6) M.