Distribution of Muscarinic Acetylcholine Receptors and Presynaptic Nerve Terminals in Amphibian Heart

At many synapses, neurotransmitter receptor molecules in the postsynaptic mem- brane are selectively concentrated at a site directly opposite the presynaptic nerve terminal . In this paper, I examine acetylcholine (ACh) receptor distribution in cardiac muscle in relation to the distribution of presynaptic axonal varicosities . The density of varicosities, stained with zinc iodide and osmium, ranges from 0.7/100 tt,m 2 in ventricle to 1.9/100 (,m2 in sinus venosus . It is estimated that 90% specificity to a single, saturable, high-affinity (Kd = 11 .1 pM at 21'C) class of binding sites . QNB binding sites are thought to correspond to ACh receptors, because muscarinic agonists compete for (3H)QNB binding and produce a hyperpolarization in the sinus venosus with the same order of potency . The concentrations of QNB binding sites in the sinus and atria are about twice those found in ventricle . The receptor density corresponds to the density of innervation measured by zinc iodide and osmium staining . Autoradiographic experiments show that (3H)QNB binding sites are distributed randomly over the entire surface of the muscle . This random distribution of ACh receptors in cardiac muscle has important implications for the function of the cardiac neuroeffector junction .