Tetrodotoxin Sensitivity of the Vertebrate Cardiac Na+ Current

Evolutionary origin and physiological significance of the tetrodotoxin (TTX) resistance of the vertebrate cardiac Na+ current (I-Na) is still unresolved. To this end, TTX sensitivity of the cardiac I-Na was examined in cardiac myocytes of a cyclostome (lamprey), three teleost fishes (crucian carp, burbot and rainbow trout), a clawed frog, a snake (viper) and a bird (quail). In lamprey, teleost fishes, frog and bird the cardiac I-Na was highly TTX-sensitive with EC50-values between 1.4 and 6.6 nmol.L-1. In the snake heart, about 80% of the I-Na was TTX-resistant with EC50 value of 0.65 mu mol.L-1, the rest being TTX-sensitive (EC50 = 0.5 nmol.L-1). Although TTX-resistance of the cardiac I-Na appears to be limited to mammals and reptiles, the presence of TTX-resistant isoform of Na+ channel in the lamprey heart suggest an early evolutionary origin of the TTX-resistance, perhaps in the common ancestor of all vertebrates.