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'Couch potato pill' might stop heat stroke too
Date:1/8/2012

associated with malignant hyperthermia, a life-threatening inherited disorder of skeletal muscle in which commonly used general anesthetics trigger uncontrolled muscle contractions and dangerous increases in body temperature. Unexpectedly, further work demonstrated that these mice exhibit similar uncontrolled muscle contractions a classic heat stroke response during exposure to high temperatures or when exercising under warm conditions.

The team found that AICAR administration protected the mice from experiencing such contractions under heat stress. If not stopped, the contractions cause muscles to break apart and release their contents, including potassium and proteins, into the blood. High levels of potassium in the blood are extremely toxic and, if not treated quickly, can cause cardiac arrhythmias and death.

Unfortunately, the drug didn't deliver the same positive result for anesthetic-induced malignant hyperthermia.

AICAR made a big splash in 2008 when a study published in Cell, a prestigious scientific journal, found that the drug built muscle and increased endurance in completely inactive mice. As additional studies further established AICAR's ability to improve muscle function, the team grew curious to test how it might influence the whole-body muscle contractions characteristic of RYR1-associated heat stroke in mice.

Not only did they discover the unanticipated protective effect of the drug, but that it worked in a completely different way than they originally thought.

AICAR normally works by activating the body's metabolic "master switch," an enzyme called AMPK that, among other things, influences muscle activity. However, researchers found that the ability of the drug to protect the mice from heat stroke was unrelated to its effects on this master switch. Rather, it directly influenced RYR1.

RYR1, or the type 1 ryanodine receptor, is a protein that plays an essential role in muscle cont
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Contact: Emily Boynton
emily_boynton@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
Source:Eurekalert

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