This finding provides clear evidence that protons, long considered a candidate substance in heart pain, are indeed the chemical messenger that activates cardiac ischemia-sensing neurons. In further studies, the lab determined the molecular identity of the ion channel that responds to protons. Of the four ASICs expressed in sensory neurons, only ASIC3 has all of the functional properties that match the native acid-gated current found in cardiac sensory neurons. These findings make ASIC3 the best candidate for being the pain sensor in cardiac neurons. Drugs directed against this channel might be valuable for decreasing both anginal pain and the sympathetic input that can worsen the condition of a diseased heart.
Central synapses are the fundamental unit of information processing in the brain.
Not surprisingly, changes in synaptic function underlie the ability to learn and remember, and disruptions of synaptic function occur in neurological diseases such as epilepsy and Alzheimer's disease. Recently members of Gary Westbrook's lab have discovered that one group of cell adhesion molecules, the integrins, play an important role in synaptic development in hippocampal neurons. The Westbrook lab used single hippocampal neurons grown in microisland cultures to explore the properties of developing synapses. They found that synapses undergo a specific pattern of maturation that is dependent on integrin-mediated signaling. However, activity at the synapse initiates a set of maturational changes that are dependent on the bridging of the synaptic cleft by integrins and the as yet unknown proteins to which they bind.