Scientists at UCSF's Ernest Gallo Clinic and Research Center discovered in an animal model of the disease that during periods of intense muscle activity, muscles remain excited too long and degenerate if the protein fails to transport the neurotransmitter acetylcholine away from the nerve-muscle synapse. Muscle degeneration is the hallmark of muscular dystrophy, one of the most common genetic diseases.
The study was carried out in the roundworm, C. elegans, an animal which has provided early clues to the role of a number of important molecules in the human nervous system. The researchers expect that the protein, which they showed is an acetylcholine transporter, plays the same role in humans as it does in C. elegans, identifying a potential new route for treatment of muscular dystrophy.
The research is being reported in the August 19 issue of the journal Nature.
Normally, a nerve cell induces a muscle cell to contract by releasing the neurotransmitter acetylcholine at the synapse -- the junction where the two cells meet. Researchers have identified transporters for most neurotransmitters, such as serotonin, dopamine and glutamate. The transporters remove neurotransmitters from the synapse, in effect providing an "off" switch to the neurotransmitter's potent effects. It was thought that normal enzymatic breakdown of acetylcholine was so effective that a transporter wasn't needed to clear excess acetylcholine from the synapse. But the scientists found that during periods of intense muscle activity, a transporter must clear acetylcholine from the synapse.
"Discovering a transporter for acetylcholine was quite a surprise," said Steven McIntire, MD, PhD, UCSF assistant professor of neurology. "Identification of an acetylcholine transporter i
Contact: Wallace Ravven
University of California - San Francisco