Differentiation of the fast Na+ channel in embryonic heart cells: interaction of the channel with neurotoxins.
The sensitivity of embryonic cardiac cells to tetrodotoxin (TTX) increases with age. At the early embryonic stage, the maximum upstroke velocity is not affected by the presence of TTX. In the course of both in ovo and in vitro development, this velocity reaches an adult-like value of 90-120 V/sec, which is decreased in the presence of TTX to 5-10 V/sec. The differentiation of the Na+ channel has been followed by using three types of specific toxins: (i) TTX or a tritiated derivative of it, (ii) a polypeptide toxin extracted from sea anemone, and (iii) the alkaloidic toxins veratridine and batrachotoxin. Electrophysiological, including voltage-clamp experiments, and biochemical studies have shown (i) that the TTX receptor and the fast Na+ channel machinery exist even when action potentials are insensitive to TTX--the channel is then in a nonfunctional or silent form that is revealed (or chemically activated) by both the alkaloids and the polypeptide toxin--and (ii) that the total number of Na+ channels increases during development by a factor of 4 or 5. In monolayers of cardiac cells insensitive to TTX in which all Na+ channels are in a nonfunctional form, the rate of degradation of the TTX receptor follows first-order kinetics with a half-time of 9 hr. In aggregates fully sensitive to TTX, the number of TTX receptors remains perfectly stable 24 hr after blockade of protein synthesis.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D003064:Cnidarian Venoms / Q000494:pharmacology; D006321:Heart / Q000196:embryology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D012964:Sodium / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D003064:Cnidarian Venoms; D007473:Ion Channels; D009498:Neurotoxins; D013779:Tetrodotoxin; C028800:toxin II (Anemonia sulcata); D012964:Sodium