Interaction of permeant ions with channels activated by acetylcholine in Aplysia neurones

Abstract

1. Aplysia neurones with an excitatory response to acetylcholine (ACh) were voltage-clamped, and the ACh-induced currents were studied using noise and relaxation techniques. The mean channel open time, tau, and the amplitude of the elementary current, iel, were determined from these experiments, and the variation of these parameters with the ionic content of the extracellular solution was analysed. The goal of this work was to test whether permeant ions may bind in a voltage-dependent manner to channel sites and thereby hinder channel closing, as has been proposed before (Ascher, Marty & Neild, 1978a). 2. The relation between tau and the membrane potential V has a similar shape in normal sea water and after total replacement of Na ions with Li or Cs. In contrast, the shape of the tau(V) relation is modified if Na is replaced by Mg, Sr, or Ba. 3. Replacing the divalent cations (Mg and Ca) present in normal sea water with Na results in a decrease of tau and an increase of iel. Both effects are enhanced by cell hyperpolarization. 4. Similarly partial replacement of Na by Sr causes a voltage-dependent decrease of iel. 5. Experiments were performed in solutions containing Na and sucrose, or Mg and mannitol. In both cases tau was smaller than in an isotonic Na or Mg solution. 6. None of the above observations can be accounted for on the sole basis of outer surface potential changes. 7. A quantitative model of the interaction between permeant ions and ACh-sensitive channels is proposed. The possible relevance of this model for the interpretation of tau(V) curves in other systems is discussed.