Molecular Pharmacology, Vol 20, 526-532, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

High-Affinity Saxitoxin Receptor Sites in Vertebrate Heart

Evidence for Sites Associated with Autonomic Nerve Endings

¹ Department of Pharmacology, University of Washington, Seattle, Washington 98195

we have studied the binding of [³H]saxitoxin (STX) to total particulate preparations from ventricles of vertebrate heart. In each of the six species studied, a single class of high-affinity receptor sites was detected with B_max values of 1.7 fmoles/mg (wet weight) to 12.0 fmoles/mg (wet weight) and K_D values of 0.3 nM-7.5 nM for STX and 3.5 nM-10.4 nM for tetrodotoxin (TTX). In the bullfrog heart, two classes of high-affinity STX receptor sites were observed. One class of sites (28%) had high affinity for TTX and resembled STX/TTX sites in bullfrog brain. A second class (72%) had very low affinity for TTX and were apparently specific to the heart. In chick heart, the high-affinity STX/ TTX receptor sites had properties similar to myocardial sodium channels studied physiologically. In contrast, for mammalian hearts, the K_D of high-affinity STX/TTX receptor sites for TTX (3.5 nM-10 nM) does not correlate with the inhibition of myocardial sodium channels by high concentrations of TTX (800 nM-3000 nM) in physiological experiments. In the rat, treatment with 6-hydroxydopamine caused a loss of 50-60% of the high-affinity STX/TTX receptor sites in the ventricles, consistent with the conclusion that a major fraction of these high-affinity toxin binding sites is associated with autonomic nerve endings in the rat. Taken together, the results show that vertebrate hearts contain a substantial complement of high-affinity STX/TTX receptor sites that are associated with autonomic nerve endings. In mammalian heart, there may be no high-affinity STX/TTX receptor sites associated with myocardial sodium channels.