December 9, 2014

Solving a paradox

IST Austria professor Peter Jonas looks into the Calcium riddle in the synapse • eLife paper explains paradox with proximity of Calcium channels and sensors for transmitter release

The transmission of information from one nerve cell to the next has long been known to have a puzzling property: the amount of neurotransmitter, the chemicals that transmit signals at the synapse from one nerve to the next, is highly dependent on the amount of Calcium in the synapse. However, the length of time during which neurotransmitter is released, the so-called time course of release (TCR), is independent of Calcium concentrations. This property was originally uncovered in the synapse between nerves and muscle cells. In their eLife paper (DOI:, Arai and Jonas show that also a synapse in the brain shows this paradoxical phenomenon. They suggest that this is probably due to Calcium channels and sensors for transmitter release being located closely together in the nerve terminals. eLife is a new open access journal that reports findings of general significance in life sciences.

The authors show that at the synapse between basket cells and Purkinje cells in the cerebellum, the time course of neurotransmitter release is largely independent of Calcium concentrations in the synapse, while the amount of neurotransmitter released is highly dependent on Calcium concentrations. Arai and Jonas explore the mechanism underlying this paradox using a realistic model of transmitter release. This shows that a very short distance between Calcium channels and release sensors, called tight coupling, may play a key role in the time course of transmitter release. Using Calcium chelators, which bind Calcium, the researchers tested whether Calcium channels and release sensors are located closely together in the studied synapse. While the fast-acting Calcium chelator BAPTA can very effectively suppress transmitter release, the slow-acting chelator EGTA works too slowly to suppress release. This finding suggests that tight coupling is at work at the synapse between basket cells and Purkinje cells. One important benefit resulting from tight coupling may be the Calcium-independence of the time course of release.