The nervous system is a highly adaptive organ. Even within a single lifetime, the ability to respond to changes in the environment is paramount to an organism's fitness. Adaptations occur on the molecular level on a regular basis; changes in the patterns of gene expression in response to environmental circumstance are the bread and butter of cellular biology. Denervation is the loss of motor innervation that controls the muscle activity; the skeletal muscle is no longer controlled by the central nervous system. The changes experienced by nerve and muscle cells resulting in denervation supersensitivity occur on the molecular level -- and primarily involve modifications in neurotransmitter activity and the density of their receptors.
The brain is a collection of neurons arranged to work together in an incredibly precise, detailed way. Because these cells do not share a common cytoplasm, they require an extracellular method of communication, in order to propagate electrical signals across space. Evolution has adopted the neurotransmitter -- which is a class of chemicals produced and released by nerve cells -- in order to communicate with neighboring nerve cells. The neurotransmitter diffuses across the space between nerve terminals, known as synaptic gaps, and eventually comes into contact with protein receptors on the membrane surface of the so-called "post-synaptic" cell. These transmitter receptors undergo a conformational change and induce a series of biochemical signals within the receiving cell. These events occur within milliseconds, and are the substrate of our thoughts, behaviors, and perception of existence.
Commonly abbreviated as Ach, Acetylcholine is a critical neurotransmitter that plays an important role in the pathology of denervation supersensitivity. This transmitter is produced and released in both the peripheral and central nervous system; It is well-known for its action in the neuromuscular junction, where it behaves as an excitatory transmitter, capable of initiating muscular contraction. Denervation supersensitivity is widely attributed to pathologic adaptations in the chemistry of this neuromuscular transmitter following denervation of skeletal muscle.
The Role of Synaptic Enzymes
According to a 1992 study from the University of California, San Francisco, supersensitvity due to denervation is partially caused by a reduction in the activity of acetylcholinesterase in the nerve synapse. This enzyme normally acts to breakdown acetylcholine, as it is released into the synaptic gap between nerve cells. Its activity ensures that the time of neurotransmitter activity is a finite, tightly controlled value. When the activity of these enzymes is diminished, the period that ACh is present in the synapse will be prolonged, thus contributing to the supersensitivity syndrome.
Denervated muscle fibers will predictably change their cellular properties, notably by up-regulating their sensitivity to acetylcholine. Specifically, these muscle cells will be induced to synthesize new acetylcholine receptors and insert them into the plasma membrane of the cell. According to a 1984 study from the Journal of Cell Biology, the levels of RNA coding for ACh receptors was increased 100 fold in denervated mouse muscles. The increased RNA levels increase the production of receptor proteins, which consequently amplify the muscle's sensitivity to acetylcholine release.
- Journal of Cell Biology: Denervation supersensitivity in skeletal muscle, analysis with a cloned cDNA probe; Merlie JP, Isenberg KE, SD Russell, and JR Sanes; July 1984
- Trends in Neurosciences: Denervation Supersensitivity; Thesieff S and Sellin LC; January 1980
- Nature: Denervation Supersensitivity in the Striatonigral GABA pathway; John Waddington and Alan J. Cross; December 1978
- Journal of Physiology; The Role of Acetylcholinesterase in denervation supersensitivity in the frog cardiac ganglion; Streichert LC and Sarget PB; January 1992
- Photo Credit Ablestock.com/AbleStock.com/Getty Images
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