The triad in a skeletal muscle fiber is composed of a centrally located T-tubule flanked on both sides by the terminal cisternae
of the sarcoplasmic reticulum. The spatial relationship between the DHP receptors and RyR1 embedded within at the T-tubules and SR membranes, respectively, has been the focus of scientific inquiry for several decades. It has been determined that voltage-induced conformational changes are responsible for sequentially activating these two receptors. The sequence of events involved in excitation-contraction coupling is somewhat analogous to falling dominoes. In this scenario, the action potential propagating along the sarcolemma initiates the sequence of events in the same way the movement of your hand does. Just as your hand pushes over the first domino, the voltage change across the T-tubule membrane causes a conformational change in the DHP receptor. The first falling domino knocking over the subsequent dominoes represents the conformational change of the DHP receptor initiating a subsequent allosteric change in RyR1. When RyR1 is activated, calcium is released from the sarcoplasmic reticulum, leading to muscle contraction. Hundreds of mutations have been identified in RyR1 that contribute to multiple muscular diseases. Assume that a new mutation was discovered that causes this receptor to continually remain open. Based on what you know about the function of this receptor, how would you expect this new mutation to impact contraction?
a. This mutation will decrease the sensitivity of the DPH receptor to voltage changes,which will prevent muscle contraction.
b. This mutation will increase the sensitivity of the DPH receptor to voltage changes, which will induce continued muscle contraction.
c. This mutation will increase levels of calcium in the sarcoplasm, which will induce continued muscle contraction.
d. This mutation will decrease levels of calcium in the sarcoplasm, which will prevent muscle contraction.
Option B. This mutation will increase the sensitivity of the DPH receptor to voltage changes, which will induce continued muscle contraction.
Explanation:
Since the receptor stays open, it allows for calcium to be released from the sarcoplasmic reticulum and thus, enables muscle contraction to take place.
