A new class of agents has been developed which alters the conductance of ion cha

Question

A new class of agents has been developed which alters the conductance of ion channels. Unfortunately, it is not clear what ion channels are being affected or what the effect is on conductance. To investigate this, you examine an isolated vertebrate nerve- skeletal muscle preparation which allows you to stimulate the nerve and examine the resulting muscle contraction.

. 1) When you add Agent Z to the fluid bath in which the nervemuscle preparation is being maintained, the muscle contracts spontaneously without you having to stimulate the nerve. However, atropine does not block this effect. What is/are the most likely target(s) and effect(s) of Agent Z?

2) Agent Q is known to increase calcium conductances.

i. What results would you expect to see when Agent Q is added to your preparation?

ii. Agent Q turns out to be ionized under normal physiological pH, such as found in your bathing fluid. Does this help determine the target/mode of action of Agent Q? If so, how?

Explanation / Answer

1). It was given that, the agent Z can induce spontaneous skeletal muscle contractions, but its effect is not blocked by the atropine. Atropine is a muscarinic acetylcholine receptor antagonist, which acts through the G-protein coupled receptors. But the skeletal muscles are innervated by the nicotinic type of acetylcholine receptors, which act through the ligand gated ion channels. So, the experiment must be repeated to test the effect of agent Z in the presence of pancuronium. Pancuronium is a nicotinic acetylcholine receptor antagonist, so, if the effect of agent Z is blocked in the presence of pancuronium means, agent Z is stimulating the nACh receptors.

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