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 EC(50)-values between 1.4 and 6.6 nmol·L(-1). In the snake heart, about 80% of the I(Na) was TTX-resistant with EC(50) value of 0.65 μmol·L(-1), the rest being TTX-sensitive (EC(50) = 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.