Identification of two sodium channel subtypes in chick heart and brain

Na+ channels in chick brain and heart have been directly compared by measuring binding of tritium-labeled saxitoxin ([3H]STX) to the two tissues under identical conditions. Maximum saturable uptake and toxin affinity were considerably less in chick heart than in chick brain, requiring the development of an assay method to resolve specific [3H]STX uptake in heart. With this method, binding to both preparations consisted of a specific saturable component and a linear nonspecific component. The equilibrium dissociation constant for [3H]STX measured in chick heart (6.2-8.8 nM) was 20-30 times higher than that measured in chick brain (0.3 nM). The dissociation rate for [3H]STX was only about twice as fast in heart as it was in brain, indicating that the decrease in toxin affinity in heart results predominantly from a slowed toxin association rate. The decreased affinity for [3H]STX found at the chick heart Na+ channel is compared with toxin-resistant Na+ channels in other preparations. The existence of two Na+ channel subtypes is proposed, with high affinity and low affinity for saxitoxin and tetrodotoxin; the significance of this classification is discussed.