Muscarinic acetylcholine receptors in the heart of rats before and after birth

Publisher Website
Google Scholar
Abstract
Atropine-displaceable binding of (3H)quinuclidinyl benzilate (QNB) to homogenates was used to identify the muscarinic binding sites in rat heart atria and ventricles and to investigate developmental changes in their concentration and binding properties between the 15th day of prenatal life and 3 months after birth. On the 15th day of prenatal life, muscarinic binding sites were already present in the heart. Their concentration increased steeply between the 15th and 19th days of prenatal development; in the atria, it remained high until the 1st day after birth and thereafter it diminished throughout the postnatal life, while in the ventricles the decrease started before the first postnatal day. The concentration of the binding sites was 1.8–3.0 times higher in the atria than in the ventricles at all time points investigated. Their affinity for QNB (the antagonist) was the same in the atria and ventricles and did not change during postnatal development (K D of 17.8 pmol/l at an infinitely low concentration of the binding sites). The binding of carbamoylcholine (the agonist) to muscarinic bindig sites was analysed in experiments with the displacement of (3H)QNB binding, assuming the presence of high- and low-affinity binding sites for agonists. The proportion between the concentrations of the two classes of agonist binding sites is close to 1:1 both in the atria and the ventricles and does not change with age. No statistical significant differences were discovered between the affinities of the high- and low-affinity binding sites for carbamoylcholine between the atria and the ventricles and between new-born and adult rats. It is suggested that the steep increase in the number of muscarinic binding sites between the 15th and 19th days of prenatal development is triggered by the arrival of nerve cells and fibres into the heart (occuring on the 14th–16th day) and that it is one of the factors responsible for the onset of effective neuro-effector transmission in the heart (21st day of prenatal development). The commencement of tonic cardioinhibitory vagal control (18th day after birth) appears unrelated to developmental changes of cardiac muscarinic binding sites.