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. Consider each set of results and reply to the questions.

a) You stimulate the nerve in the presence of Agent X and the muscle contraction is stronger and more prolonged than when the agent is not present. There is no change in the muscle when exposed to Agent X in the absence of nerve stimulation.

i) What channels might be affected and how?

ii) Design experiments which could differentiate between the options you have listed.

b) When you add Agent Y to the fluid bath in which the nerve-muscle preparation is being maintained, the muscle contracts spontaneously without you having to stimulate the nerve. When atropine is applied to the fluid bath, however, the muscle does not react to the presence of Agent Y.

i) What is/are the most likely targets and how are they being altered by Agent Y?

ii) Design a set of experiments to determine the actual target and effect of Agent Y

c) Agent Z also causes spontaneous contraction of the muscle. However, atropine does not block this effect. What is/are the most likely target(s) and effect(s) of Agent Z?

d) 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?