| Nov 09, 2010 |
The cellular basis of neural impulse transmission
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(Nanowerk News) Information coded as impulses is transferred from one neuron to its target at synapses. At these close neuron-neuron contacts the impulse opens voltage sensitive calcium channels allowing the influx of calcium ions (Ca2+) and this ion then acts as a 'second messenger' to trigger the release of neurotransmitters by the fusion of a secretory vesicle with the surface membrane.
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Thanks to TWRI's Dr. Elise Stanley, it is now established that the relationship between the calcium channel and the secretory vesicle is very intimate, so much so that the fusion of a secretory vesicle can be triggered by the plume of Ca2+ entering through a very closely situated single calcium channel ("N-type Ca2+ channels carry the largest current: implications for nanodomains and transmitter release").
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There was, however, one major mystery. Since the ability of the single channel to trigger transmitter release is directly proportional to the amount of Ca2+ that enters, the largest calcium channel species--the L type (a member of the CaV1 family)--would be predicted to serve this role for transmitter release. Yet this function is almost always served by the intermediate sized, CaV2 (N type), family channels. Since calcium channel families were originally characterized under highly non-physiological conditions, Dr. Stanley and her team set out to test if these channels exhibit different properties under physiological ion conditions.
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A detailed analysis of Ca2+ entry rates for all three calcium channel families with physiological Ca2+ demonstrated that the CaV2 family representative exhibits the largest conductance, explaining its selection at the presynaptic terminal. In collaboration with Victor Matveev (New Jersey Institute for Technology), mathematical modeling showed that Ca2+ influx through a single member of this family is sufficient to trigger the fusion of a secretory vesicle located 25 nm from the channel.
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Explains Dr. Stanley, "These findings may help to explain why nature evolved this new family of channels, permitting an efficient transmitter release mechanism with a modular molecular organization. Our next objective will be to determine how this exquisitely organized 'molecular machine' plays a role in synaptic modulation which is critical for memory and behaviour modification."
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Since transmitter release is involved in virtually every aspect of nervous system function these results have a very broad impact for the understanding of normal brain processing and, in turn, a variety of central and peripheral nervous system disorders.
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