Calmodulin regulation of the cholinergic receptor in the rat heart during ontogeny and senescence

Abstract

The contents of calmodulin and cholinergic muscarinic receptor binding sites in the hearts of fetal, adult and aged rats have been examined. A biphasic pattern of calmodulin development was observed. A relatively high level of calmodulin appeared on gestational days 14–15 followed by a steady but significant decrease at birth and during the first week of postnatal life. The level of calmodulin then increased significantly during the first month followed by a decrease at 6 and 26 months of age. Calmodulin contents were significantly higher in the atrium than in the ventricle in the age groups of 1–26 months. The number of [ 3H] QNB binding sites showed a steady increase during the gestational periods studied, reaching a peak at 9 days after birth and followed by a significant ( P < 0.05) decline at 6 and 26 months of age. A good correlation between the levels of [ 3H]. QNB binding and calmodulin was observed from day 9 of the postnatal period to 26 months of age. In the presence of calcium, calmodulin induced a dose-dependent receptor binding loss in the hearts of postnatal, young adult and aged rats under phosphorylating conditions. These findings support the suggestion that calmodulin may regulate cholinergic functions during ontogeny and senescence.