Biology Reference
In-Depth Information
Assume that we would like to find evidence supporting the hypothesis
that the inhibitor A is connected with B in a network similar to that
shown in Figure 10-14 (right panel). We can try to monitor the system
response to neutralization of the action of A (A-receptor blocker) or
removal of A (antibody infusion) from the system. Because the model
predicts gradual pulse shrinking toward the steady-state level
(Figure 10-19), a similar experimental outcome would indicate system
connectivity like that shown in Figure 10-14. As another example, we
might be seeking support for the hypothesis that stimulator A is
connected with B as shown in Figure 10-14 (left panel). In this case,
administering a large, constant infusion of A should clamp the
oscillations (by exceeding the action threshold, resulting in continuous
response from the target organ). The latter concept is shown in
Figure 10-22, which depicts a computer-generated prediction of the
system response to infusion of hormone A [assuming that A stimulates
B: Eq. (10-15)]. We simulated constant low (left panel) and high
(right panel) infusion of A by increasing the basal A-secretion from
zero to 3 or 6, starting at t
¼
97 [see Section IV, Part C.3 and
Eq. (10-21)].
The model predicts gradual pulse shrinking toward the current
steady-state level (the latter depends on the infusion rate). If exogenous
A is sufficiently high (right panel), the pulses disappear. Similar
outcomes observed in real experimental setting would suggest that
A and B are connected as shown in Figure 10-14 (left panel).
This approach has limitations, however. These experiments cannot
disclose whether A is actually involved in a feedback with B, or acts
merely as a trigger to remove a certain subsystem from its steady state.
For example, consider the two networks shown in Figure 10-23, and
suppose only the concentrations of hormone B can be measured.
Assume that E stimulates B and its removal diminishes the secretion of
B. Because endogenous E cannot be assessed, we have no direct means to
FIGURE 10-22.
System response to exogenous constant administration of the stimulating hormone A (black line).
The plots show simulation of low (left panel) and high (right panel) infusion of A starting at t ¼ 97.
