Prolonged activation of β 1 adrenergic receptors (β1AR) in the heart ultimately impairs ventricular function, contributing to the development of heart failure. The paper you just read (Perez et al, Nature Medicine 2003) says that the Arg389 polymorphism of
the β1AR confers a predisposition to developing heart failure in humans and in animal models. The presence of Arg389 is associated with enhanced agonist -induced contractility in hearts from young (3mo) mice, and decreased responses to agonist in
older (6 mo) mice (Figure 1). Further studies showed that this was not due to decreased levels of Arg389 β1AR.
In the discussion, the authors suggest that enhanced β1AR signaling in younger Arg389 mice turns on a program that ultimately leads to decreased sign aling and heart failure. They further suggest that these changes are specific to β1AR signaling. They propose that changes in Gαs, GRK - 2, or type V adenylyl cyclase might be responsible for the loss of β1AR signaling in
older Arg389 mice. Design an experiment to test the role of one of those players in causing or contributing to the loss of β1AR signaling in older Arg389 mice.
This is an interesting concept and worth investigating.
The question asks for an experimental design. So, you must first come up with a hypothesis and null-hypothesis.
GRK-2 increases due to aging in mice is responsible for the loss of Beta 1AR ...
The expert designs an experiment to act as a follow-up on a specific cardiac-related outcome.