Investigating the Cocaine-induced Reduction of Potassium Current on the Generation of Action Potentials Using a Computational Model

INTRODUCTION: Drugs of abuse, such as cocaine, affect different brain regions and lead to pathological memories. These abnormal memories may occur due to changes in synaptic transmissions or variations in synaptic properties of neurons. It has been shown that cocaine inhibits delayed rectifying potassium currents in affected brain regions and can create pathological memories. This study investigates how the change in the conductance of delayed rectifying potassium channels can affect the produced action potentials using a computational model. METHODS: We present a computational model with different channels and receptors, including sodium, potassium, calcium, NMDARs, and AMPARs, which can produce burst-type action potentials. In the simulations, by changing the delayed rectifying potassium conductance bifurcation diagram is calculated. RESULTS: By decreasing the potassium current for a fixed stimulatory signal, burst-type action potentials can be generated. In the following and with a further reduction of potassium conductance, produced action potentials exhibit non-linear and even chaotic behaviors. CONCLUSION: Results show that for a specific range of potassium conductance, a chaotic regime emerges in produced action potentials. These chaotic oscillations may play a role in inducing abnormal memories. HIGHLIGHTS: Cocaine consumption reduces the potassium current in affected cells. Decreasing the potassium currents elicits burst action potentials. Produced bursts might have chaotic behaviors. Chaotic oscillations might be related to the toxic effects of cocaine. PLAIN LANGUAGE SUMMARY: Drugs of abuse such as cocaine can manipulate brain circuits and may form some pathological memories. These memories can lead to long-term addiction. Furthermore, these drugs also can have toxic effects on the cells. Researchers are looking for the mechanisms that can lead to abnormal memories and toxic effects of drugs. It seems that an efficient mechanism that can be used by drugs of abuse is the manipulation of potassium currents in the affected cells. Here, in a computational model, we have shown that changes in the conductance of delayed rectifying potassium channels can lead to nonlinear and even chaotic behaviors in the produced action potentials. These behaviors might have a role in drug toxic effects.