For release: Monday, June 17, 1991
Scientists supported by the National Institute of Neurological Disorders and Stroke (NINDS) have invented a tiny, ultra-sensitive electrode that can record, for the first time, the millionths-of-a-second-long burst of catecholamine molecules as they erupt from the surface of a single cell. Catecholamines are used by some cells as neurotransmitters, or molecules that allow nerve cells to communicate between themselves and with other kinds of cells.
The new electrode — developed under the direction of an NINDS grantee, Kenan Professor of Chemistry R. Mark Wightman, Ph.D. of the University of North Carolina at Chapel Hill — will make possible more detailed studies of the mechanisms that regulate the release of neurotransmitters, the scientists say. Such studies may lead to an increased understanding of brain function and the creation of new drugs to treat neurological diseases, they add.
In the past, scientists have been able to detect the release of neurotransmitter molecules no sooner than a full second after the event, making it impossible to observe how quickly the molecules are released under different conditions. The new electrode detects the presence of catecholamines in 6 microseconds. Wightman's report appears in the June issue of the Journal of Neurochemistry .*
The electrode is also one of the most sensitive chemical detectors ever built. "As an analytical chemist I'm really excited by this because we can detect the presence of approximately 10 million molecules, which is about one millionth of one billionth of a gram," Wightman says. Such sensitivity is otherwise possible only with laser spectroscopy,but has not been accomplished at the level of the single cell.
In the recent experiments Wightman measured the release of catecholamines from a cell taken from the adrenal gland. The adrenal cell is closely related to the neuron and is often used as a model for the neural cell. Now that he has developed the technique, Wightman will next use it to measure the release of catecholamines from neurons.
The electrode can be a powerful tool for finding how drugs and substances naturally found in the brain affect neural transmission. "What we hope to do is discover the biochemical steps that lead to the release of the neurotransmitter," Wightman says. For example, the electrode could determine if cells delay or accelerate the release of neurotransmitters when a chemical compound or another neurotransmitter is present. The technique could also be used to find how neurotransmitter release is affected when scientists tinker with the machinery of the cell through genetic engineering.
Wightman hopes that the technique will lead to new therapeutic drugs or new information about how old drugs work. "The more basic knowledge you have about how the system functions, the greater your ability to intervene," Wightman says. Scientists often know that certain compounds work in the brain but don't know why. Knowledge about how drugs work could lead to the development of better drugs with fewer side effects. Drugs for Parkinson's disease, for example, often have undesirable side effects. Dopamine, the neurotransmitter most closely involved with Parkinson's disease, is one of the catecholamine-type neurotransmitters that can be monitored with the electrode.
Wightman's data also lend support to the theory that neurotransmitters are stored in the cells in bubble-like vesicles containing about 10 million molecules each and released in discrete packets as the vesicle opens. This theory has long been assumed to be valid, but without direct evidence, Wightman says. Scientists have never before been able to show that neurotransmitter molecules are released in bursts, as they would be if a packet of molecules inside the cell suddenly opened up at the cell surface. Wightman, on the other hand, can observe exactly this phenomenon with the electrode.
W. Watson Alberts, Ph.D., deputy director of the NINDS Division of Fundamental Neurosciences, notes that "the ability to directly measure the release of minute amounts of neurotransmitters in real time is an important new development which will allow better understanding of the factors that regulate neurotransmitter release."
The National Institute of Neurological Disorders and Stroke, one of the 13 National Institutes of Health in Bethesda, Maryland, is the primary supporter of brain and nervous system research in the United States.
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* David J. Lexzczyszyn et al. "Secretion of Catecholamines from Individual Adrenal Medullary Chromaffin Cells." Journal of Neurochemistry, Vol. 56, No. 6, 1991, pp 1855-1863.
Last Modified August 7, 2009