Cardiac Muscarinic Receptors in Conotruncal Abnormalities

Cranial neural crest contributes to aorticolpulmonary septation as well as to the parasympathetic innervation of the heart. To determine whether parasympathetic innervation of the heart is altered in a human conotruncal abnormality (Tetralogy of Fallot; TOF) which may be caused by a neural crest defect, muscarinic receptors were studied in atrial appendage tissue obtained during corrective surgery. Tissue from children with TOP was compared with tissue from children with a defect not involving the aorticopulmonary septum (secundum atrial septal defect; ASD). Muscarinic receptor density (Bmax) and antagonist affinity (KD) were determined using [3H]3-quinuclidinylbenzilate ([3H]QNB). Agonist binding properties were determined in carbamylcholine (Carb)/[3H]QNB competition studies. Carb binding was resolved into high and low affinity components characterized by. KH and KL, and by RH, the fraction of receptors displaying high affinity binding. No differences were seen in TOP and ASD atria KD in nM, KH and KL in uM, Bmax in pmol/mg protein. Thus, there is an apparent dissociation of the consequences of depletion of mesenchymal vs neural crest in TOF. Alternatively, the neural crest insult which causes TOF may not be of sufficient magnitude to affect cardiac muscarinic receptors.