The effects of amyloid peptides on A-type K(+) currents of Drosophila larval cholinergic neurons: modeled actions on firing properties.

In a previous paper we described the actions of beta-amyloid on an A-type K(+) current from Drosophila 3(rd) Instar larval neurons. The results were a depolarizing shift in the steady-state voltage dependence of inactivation and an increase in the rate of recovery from inactivation of the current. In this work we have used the simulation program NEURON to construct a model cell. We then use the model to predict the effects of changing the A-type K(+) current as was observed in the amyloid treated neurons on the firing properties of the cell. We show that changing the steady-state voltage dependence of inactivation of the current to a more depolarized level as observed in experiments in beta-amyloid treated neurons causes an increase in the threshold for the initiation of repetitive firing. However, increasing the rate of recovery from inactivation had no effect. Changing both properties simultaneously had no additional effect over changing the voltage dependence of inactivation alone. Thus, a change in the steady-state properties of the A-type K(+ )current as seen in the amyloid-treated Drosophila cholinergic neurons is sufficient to alter the firing properties of the modeled cell.