You are studying a new virus whose effects include loss of motor control in all

Question

You are studying a new virus whose effects include loss of motor control in all limbs due to an imbalance of intracellular potassium ions. You discover that this is due to viral induced depolarization of nerve membranes, resulting in constitutive activation of the voltage-gated K+ channel. You begin to design drugs that will stop the passage of K+ ions through this channel. Based on your mechanistic knowledge of the physical characteristics and mode of regulation of the voltage-gated K+ channel, describe two strategies whereby new drugs could inhibit K+ ion flow through this channel.

Explanation / Answer

Selectivity filters located in the transmembrane pore region could be a target of inhibition. In the K+ voltage-gated channel, there is an amino acid sequence (Thr-Val-Gly-Tyr/Phe-Gly) that acts as a filter for K+ ions.

Voltage sensing domains (VSD) such as S4 alpha-helix with positive amino acid residues and S5-S6 subunits could also be a target of inhibition.

Drug-mediated induction of N-type inactivation of K+ channels leads to closed confirmation, that results of forming a ball like structure at N-terminal that will tether to rest of the protein and closes the pore to prevent movement of K+ ions. So this N-terminal must be overexpressed by drugs.

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