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

Abstract

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.

Prostaglandin E2Promotes Nav1.8 Trafficking via Its Intracellular RRR Motif Through the Protein Kinase A Pathway

“…The time constant for activation (τ m ) and inactivation (τ h ) kinetics of the Na v 1.8 current in prolonged PGE 2 ‐treated or control DRG neurons was estimated using Hodgkin–Huxley type fits to the currents elicited with depolarizing test pulses to voltages ranging from −30 to 40 mV (Figure 1C). To evaluate the contribution of the change in the channels' electrophysiological properties to the Na v 1.8 peak current after treatment, we used a computer model in which the biophysical properties of Na v 1.8 channels were inserted into a single section soma with a surface area of ∼2000 µm 2 (23,24). The maximum conductance ( G max ) of Na v channels was set to 0.01 S/cm 2 , and the eruptional potential of Na + was +50 mV.…”

Modeling the complex pathology of Alzheimer's disease in Drosophila

“…Although not a transgenic model, the treatment of primary cholinergic larval neurons with Aβ42 preparations altered the properties of A-type K + currents (Kidd et al, 2006; Kidd and Sattelle, 2006). A recent study also described the selective degradation of Kv4 channels in flies expressing Aβ42 leading to neuronal hyperactivity (Fig.…”

Differential expression of voltage-gated K+ currents in medial septum/diagonal band complex neurons exhibiting distinct firing phenotypes

“…Some K + channels, such as the K v 3.1 of medial septal GABAergic neurons may contribute to hippocampal theta activity through the regulation of transmitter release from axonal terminals (Henderson et al, 2010). Furthermore, I KD and I A currents have been associated with Alzheimer’s disease pathogenesis, contributing to brain dysfunction and cell death mechanisms (Angulo et al, 2004; Colom et al, 1998; Kerrigan et al, 2008; Kidd et al, 2006; Kidd and Sattelle, 2006; Pannaccione et al, 2007; Plant et al, 2006; Ye et al, 2003; Yu et al, 2006). Thus, the characterization of K + currents in medial septal neurons is necessary to understand the septo-hippocampal function as well as devastating disorders such as Alzheimer’s disease.…”