What would happen if the G-protein coupled receptor in heart cells that binds to ACh had a mutation that caused it to bind more tightly to the G-protein alpha subunit?

Question

A.  G-protein activation and K+ channel opening would happen more quickly. Heart rate may remain abnormally low, impairing response to stress.
B.  This would lead to K+ flow out of heart cells, causing increased hyperpolarization.
C.  G-protein activation and K+ channel opening would be slowed. Heart rate may remain abnormally high, especially following stress.
D.  This would lead to K+ flow into heart cells, causing increased depolarization.


Clarify Question
· What is the key concept addressed by the question?
· What type of thinking is required?

Gather Content/Choose Answer
· What do you already know about G-proteins? What other information is related to the question?

Reflect on Process
· Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?

Answer 1

C.  G-protein activation and K+ channel opening would be slowed. Heart rate may remain abnormally high, especially following stress.


Clarify Question
· What is the key concept addressed by the question?
        o Heart problems caused by a mutation in a G-protein coupled receptor.
· What type of thinking is required?
        o Answering this question correctly depended not only on distinguishing between the different components of a G-protein coupled receptor signaling pathway, but also analyzing what types of defects would occur if parts of the pathway were interrupted.

Gather Content/Choose Answer
· What do you already know about G-proteins? What other information is related to the question?
        o To solve this problem, you’ll need to know that G-protein coupled receptors do not have an ion channel themselves. Instead, following the binding of a ligand to its receptor, a G-protein is activated which then opens up separate ion channels. In heart cells, when ACh binds to it receptor, G-proteins are activated which then open up potassium channels. Recall that the concentration of potassium is greater inside the cell, so that when ion channels are opened, potassium ions will flow out of the cell down their concentration gradient. As this happens, the cell will be hyperpolarized, slowing the heart rate. If the G-protein was bound more tightly to the receptor, it would be less able to activate the potassium channels. This would depolarize the cell, leading to contraction and increased heart rate.

Reflect on Process
· Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?
        o If you figured out the correct answer, great! If not, where did you go wrong? Did you think that the potassium channel was binding to the G-protein more tightly (which would leave the channel open, hyperpolarizing the cell and slowing heart rate)? If so, it was easy to misread this question, but it states that the G-protein coupled receptor had the mutation and not the channel. Binding to the receptor would make it harder to get to the ion channel such that the channel would be closed much of the time, which would depolarize the cell and increase heart rate. Did you get confused about the concentration gradient of potassium across the membrane? Potassium is more concentrated inside the cell compared to extracellular fluid, and thus will flow out of the cell when ion channels are opened.