Interactions between anemone toxin II and veratridine on single neuronal sodium channels.
The nature of the known positive cooperativity between alkaloid and alpha-polypeptide toxins on macroscopic sodium currents was studied at the single-channel level. We have previously characterized the single-channel function of veratridine (VTD)-modified and anemone toxin II (ATX)-modified channels from lobster leg nerve. VTD and ATX are known to potentiate each other's effects in stimulating 22Na flux into vesicles containing sodium channels from lobster leg nerve. These channels, therefore, provided an excellent model for further investigation of the interactions between the toxins. A variety of such interactions were found, some of which would contribute to the positive cooperativity between these toxins. These included first, a decrease in the frequency of occurrence, but not in the lifetime, of the long channel closed state (minute range). This effect resulted in a hyperpolarization shift of the voltage dependence of the overall channel fractional open time. The second effect was a decrease in the apparent-unbinding rate of ATX at -60 mV. These interactions, which could not have been predicted by the effects of the individual toxins, were observed at negative but not at positive potentials, and led to increases in sodium channel currents. Some of the observed interactions could not contribute to the positive cooperativity between these toxins. These included the elimination of the high-conductance state of ATX-modified channels, the predominance of the VTD effect on the voltage dependence of the fast-process, the predominance of the ATX effect on the rate of decay of sodium currents at +60 mV, and the resulting intermediate toxin effect on the level of the noisy open state.
Castillo
C
C
Instituto de Estudios Avanzados (IDEA), Caracas, Venezuela.
Piernavieja
C
C
Recio-Pinto
E
E
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D003064:Cnidarian Venoms / Q000494:pharmacology*; D004553:Electric Conductivity; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008121:Nephropidae; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology*; D012615:Sea Anemones; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014701:Veratridine / Q000494:pharmacology*
D003064:Cnidarian Venoms; D009498:Neurotoxins; D015222:Sodium Channels; C028800:toxin II (Anemonia sulcata); D014701:Veratridine; D012964:Sodium