IN SILICO STUDY OF THE CORTICAL NEURON REVEALS VASOCONSTRICTIVE EFFECTS OF COCAINE MODULATES THE FIRING PATTERNS BY INHIBITING SMALL CONDUCTANCE CALCIUM‑ACTIVATED POTASSIUM CURRENT

The vasoconstrictive effects of cocaine modulate the neuronal firing patterns which could contribute to Parkinson's disease (PD). This quantitative study investigates action potential (AP) oscillation patterns of cortical neurons towards the cocaine exposure. This single compartmental in silico model comprises the sodium channel, potassium channel, calcium channel, and calcium diffusion mechanisms. Cocaine exposure (1 mg/kg to 10 mg/kg) profile is reflected as the conductance of small calcium-dependent potassium (SK) channel. First, we simulated the current-voltage profile of the SK ion channel with respect to cocaine stimulus under the voltage clamp protocol. It showed the continuous decrease of outward current because of multiple doses of cocaine from 1 mg/kg to 10 mg/kg. Then, the altered SK ion channel outward current is incorporated into the whole-cell model to investigate the AP firing patterns. The frequency of the firing patterns is elevated for the cocaine dose of 10 mg/kg after the injection of the current stimulus. Few SK ion channels are activated across the membrane and it reduced the whole cell outward current, which elevated the cell's excitability for AP generation. Our in silico study suggests the inhibitor of Ca2 + channel as new pharmacological target for bringing the normal firing patterns in cortical neurons, which are affected by cocaine.