Biochemical Strategies for Ultrarunning—Draft Version
|Written by Bruce R. Copeland, PhD|
|Wednesday, 14 May 2008 15:49|
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Appendix B: The Biochemistry of Nerve Signaling
Nerves consist of networks of neurons. Neurons are highly elongated single cells that are specialized to transmit signals in the form of electrical activity over long distances (as much as a meter) to one or more target cells. A typical neuron consists of a cell body, a number of dendrites that are offshoots of the cell body, and a typically longer axon region that extends from the cell body to the target cell(s). The cell body contains the nucleus, ribosomes, and most of the standard cell organelles besides mitochondria. The dendrites are long tubes that provide sites for stimuli from other cells. The axon transmits the nerve's electrical signal over a long distance and usually makes branches to multiple target cells near its end (for example all the muscle cells in a muscle).
The junctions between stimulating cells and neuronal dendrites and between the neuronal axons and target cells are called synapses. There are many different types of synapses, but in most cases the originating cell releases some kind of neurotransmitter, such as acetylcholine. When a nerve cell is the stimulating cell, the neurotransmitter is released in response to the nerve cell's electrical signal. After release, the neurotransmitter diffuses across the short space between cells at the synaptic junction. When the neurotransmitter arrives at the target cell membrane, it binds to a receptor on the target cell, which precipitates electrical activity in the target cell. The mechanism of neurotransmitter release typically involves some kind of membrane rearrangement that has very specific requirements for concentrations of sodium, calcium, and magnesium ions on the inside and outside of the neuronal cell membrane. For example, when magnesium ion is insufficient at the junction between a motor neuron and a muscle cell, the junction (and therefore the target muscle cell) is hyperexcitable.
The electrical signal propagated by a nerve cell is called an action potential. Membranes in all cells typically have some kind of normal polarization that results from differences in ion concentrations on the two sides of the membrane. This normal polarization gives rise to what is called a resting potential. In nerve cells, there is a resting potential of about -70 millivolts (outside negative). This resting potential results from the fact that nerve cells maintain a much higher concentration of potassium ion inside the cell than is found outside and a somewhat lower concentration of sodium ion inside the cell than is found outside. These concentration differences are maintained by special cell membrane proteins that consume ATP to pump sodium out and potassium in. Nerve cell membranes also contain large numbers of voltage-gated channels. These channels allow specific ions to flow across the membrane only when the membrane becomes sufficiently depolarized and then only for a very brief period of time. There are voltage-gated sodium channels and voltage-gated potassium channels. When a neurotransmitter binds at the dendritic synapse of a nerve cell, the binding briefly opens other pores that cause a transient depolarization of the membrane. This depolarization opens the voltage-gated channels in the vicinity of the synapse and generates a further depolarization. Because of the specificity of the channels for specific ions, the membrane potential actually reverses direction. This reversal in electrical potential is the action potential. The voltage gating of the channels, their unique timing, and the continued pumping of sodium and potassium ions by the ATP driven pump causes the action potential to be very short-lived but to travel rapidly down the length of the nerve cell.
Nerve cells require large amounts of ATP to drive their sodium/potassium ion pumps. This ATP is mostly produced by nerve cell mitochondria. Nerve cell axons have special structures called microtubules along which the mitochondria are spaced to ensure that ATP is readily available over the entire length of the axon. Nerve cell mitochondria also play an important role in sequestering calcium ions. This is critical in the vicinity of the terminal axon synapses.
Muscle cells have some of the same features as nerve cells. They receive their signal to contract from nerve cells, so they have an incoming synapse. They also propagate the signal to contract as an action potential, and therefore require ATP driven sodium/potassium ion pumps and voltage-gated ion channels.
A number of things can go wrong in nerve cells. Action potentials depends on the presence of appropriate sodium and potassium ion concentrations on the inside and outside of the nerve cell membrane. Shortages of either of these ions can interfere with proper development and propagation of action potentials or can cause the cell to waste unnecessary energy maintaining ion gradients. In addition, appropriate concentrations of calcium and magnesium ions are critical at nerve synapses. Inadequate carbohydrate stores, inadequate electrolytes, or inadequate quinone pools can lead to mitochondrial damage and destruction, just as in muscle cells. This rarely becomes serious enough to cause nerve cell destruction itself, but it can seriously harm action potential propagation whenever a critically spaced mitochondrion in the axon ceases to function.