Posted by raybakes on November 18, 2004, at 6:48:42
Article on neuron energy needs and what happens when energy falls too low..
DEATH OF A NEURON Several cellular insults, including mutations, toxins, and lack of oxygen, can induce mitochondrial failure, but the end result is the same: too little energy to meet the cell's demands. Most cells store glycogen and can derive some energy from glycolysis, but neurons are particularly susceptible to damage from low levels of ATP, owing to their high energy needs and almost exclusive reliance on mitochondria for energy.
ATP-driven ion pumps maintain neurons in a low-calcium state; the resulting calcium gradient is essential for the calcium signaling that plays such an important role in neuronal function.3 When calcium enters the cell, the mitochondria act as temporary reservoirs until the ion pumps can lower intracellular calcium to their usual levels. Without sufficient ATP to drive the pumps, however, mitochondrial calcium levels become excessive,4 further impairing the mitochondria and leading to intracellular accumulation of ROS. "Mitochondria cannot work in a high calcium environment," Nicholls explains.
ATP also functions in sequestering neurotransmitters such as glutamate in synaptic vesicles. When the neuron receives an impulse, these vesicles release glutamate into the synapse, where it triggers a calcium influx. The cell then quickly takes up the glutamate, thus removing the stimulation from the synapse and allowing neuronal calcium levels to normalize. But in a low-ATP state, glutamate remains in the synapse indefinitely, which exacerbates already-elevated calcium levels, increases ROS levels, and further impairs the mitochondrion.5
Eventually the calcium overload and excess ROS kill the cell. Tim Greenamyre, professor of neurology and pharmacology at Emory University, says that whether the cell dies by apoptosis or necrosis depends on how quick and severe the damage is. "It's like most insults. If you slam it they die from necrosis," he says. "If you don't, they get their affairs in order and commit suicide."
THE WEAKEST LINK When mutations severely impair mitochondrial proteins, the resulting diseases appear early and impact almost every cell type. That is not the case, however, with milder mutations. "It's a threshold process," Dykens explains. "As long as there is minimal energy [from ATP] then the person may be impaired but not ill." In these cases, he says, the disease may not appear until later in life, as in Parkinson and Alzheimer diseases. "In one cell or another, mitochondrial capacity can't keep pace with demand," he says, and disease results.
poster:raybakes
thread:417331
URL: http://www.dr-bob.org/babble/alter/20041108/msgs/417331.html