ACTIONS OF THE HISTRIONICOTOXINS AT THE ION CHANNEL OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR AND AT THE VOLTAGE-SENSITIVE ION CHANNELS OF MUSCLE MEMBRANES

  • 1 January 1982
    • journal article
    • research article
    • Vol. 21  (2) , 351-361
Abstract
Various histrionicotoxins isolated from Dendrobates histrionicus tested on frog nerve-muscle preparations showed a qualitative family resemblance to one another. They blocked the nerve-evoked muscle twitch and depresssed both the peak amplitudes and the decay time constants of end-plate currents. During repetitive stimulation they progressively decreased the rate of rise and prolonged the falling phase of muscle action potentials, the latter resulting, at least in part, from blockade of voltage-sensitive K+ channels. Evidently, the histrionicotoxins act at 3 membrane channels: the channel associated with the acetylcholine receptor, the Na+ channel and the K+ channel. Study of perhydrohistrionicotoxin suggested either 2 topographically distinct sites of action at the acetylcholine receptor-ion channel complex, or 1 site and 2 ion channel complex conformations. One site or conformation only alters the kinetics of channel closure. As these sites become saturated, the end-plate current decay time constant asymptotically approaches a limiting value. The other site or conformation prevents the channel from opening altogether. Further analysis indicated that the binding site for perhydrohistrionicotoxin that alters the kinetics of channel closure has an affinity constant of 0.1 .mu.M-1 at -90 mV and that this affinity may be sensitive to the membrane potential. The lipid protein interface is a suggested site, of histrionicotoxin action, common to the 3 channels and other intrinsic membrane proteins affected by histrionicotoxins.

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