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ICE Lec 2 EK Book 2 Q32
#1 Posted : Thursday, July 05, 2018 10:07:53 PM
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A student posed this question to me, in reference to ICE for Lecture 2 in EK Study Guide 2:

"Upon reviewing the ICE aforementioned in the subject line, I’m having a problem with the suggested solution for question 32. The last line tells us that experiment 2 shows that GCAP 2 is inhibited at lower levels than GCAP 1. How can we see that from the graph if GCAP 2 is not present in the study?"

While the reasoning for the question presented in the back of the book is correct regarding why A (compensatory increase in GCAP2) is correct and sound, I understand the confusion as to how we are able to make inferences on GCAP2 if it is not explicitly measured in the study.

Experiment 2 plots RetGC activity vs. Calcium concentration.

RetGCs are activated by GCAPs. So, when GCAP activity is high, RetGC activity should also be high. At low levels of Ca, GCAP activity is higher, and so RetGC activity is also higher.

The wording in the explanation could use some improvement -- it means to say that GCAP2 is inhibited at relatively lower levels of Ca than GCAP1.

We can see this because at low Ca levels, the mice with no GCAP1 (GCAP1-/-) still produce equivalent RetGC activity to the wild type mice. The best explanation for this is that GCAP2 can "make up the difference" created by a lack of GCAP1; since that is the only GCAP present in the GCAP1-/- mice. So, you can think of the "GCAP1-/-" mice as being "GCAP2 ONLY" mice.

Farther to the right in the graph, as Ca concentration increases, the GCAP1-/- mouse is unable to "keep up" it's RetGC activity when compared to the wild type mouse. It must be that it can't "keep up" because it's ability to compensate using GCAP2 (i.e. its only available mechanism to stimulate RetGC) is reduced at higher concentrations of Ca. The wild type mouse, which contains both GCAP1 and GCAP2 in plentiful amounts, is able to activate its RetGC at higher levels due to the only advantage it has over the GCAP1-/- mouse, which is the presence of GCAP1.

Therefore, GCAP2 must be "failing" at higher Ca concentrations, as seen by the GCAP1-/- aka "GCAP2 ONLY" mouse's inability to activate RetGC at similar levels to wild type mice which contain both GCAPs at higher Ca concentrations.
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