Silinksy, Eugene, PhD

Information

Name

Silinksy, Eugene, PhD

Title

Professor and Chair

Email

e-silinsky@northwestern.edu

Office Phone

312-503-8287

Office Fax

312-503-0796

Department

Molecular Pharmacology and Biological Chemistry

Office

Searle 8-477 Chicago

Areas of Research

Mechanisms of Drug Action, Molecular Neuroscience, Signal Transduction

NU Scholar Profile

https://northwestern.pure.elsevier.com/en/persons/3238ab78-b29d-4732-b009-c02f67279e98

Recent Publications on PubMed

http://www.ncbi.nlm.nih.gov/pubmed?term=Silinksy%2C%20Eugene%5BFull%20Author%20Name%5D&cmd=DetailsSearch

Current Research

Current Research

<strong>Mechanisms of Synaptic Transmission</strong>
Nerve endings communicate with their receiving cells by the secretion of primary neurotransmitter substances and the co-release of neuromodulatory substances. The main interests of my laboratory are the mechanisms underlying the secretion and effects of neurotransmitter substances with current emphasis on the processes by which co-released adenosine derivatives modulate or mediate excitatory synaptic transmission.
We are currently focusing on presynaptic events. Earlier results from this laboratory have demonstrated:

the release of adenosine derivatives from motor nerve endings,
the presence of specific adenosine receptors on motor nerve endings and
the inhibition of neurotransmitter secretion by adenosine.

In the past few years, we have been able to measure nerve terminal calcium currents simultaneously with the electrophysiological correlates of evoked acetylcholine (ACh) release. Adenosine does not affect the calcium current that mediates ACh release in the frog and inhibits ACh release evoked by methods that bypass active calcium channels (e.g. calcium containing lipid vesicles) with a very brief latency. These recent results confirm our published suggestions beginning in 1981 that adenosine and other neuromodulators may inhibit neurotransmitter release downstream of calcium entry, and, that G proteins can inhibit transmitter release apart from changes in soluble second messenger substances. In the mouse, our recent results demonstrate that adenosine decreases calcium currents in motor nerve endings but this effect is targeted to the secretory apparatus as cleavage of the strategic plasma membrane secretory protein syntaxin prevents the effects of adenosine on calcium currents. We are currently contining our work using botulinum toxins in conjunction with knockout mice in which important parts of the secretory apparatus have been deleted to determine the specific presynaptic targets for the effects of adenosine.
This effect of adenosine has considerable physiological significance as we have shown that the neuromuscular depression that occurs during repetitive nerve stimulation at normal levels of ACh release is due to the neurally-evoked release of ATP, which after degradation to adenosine acts as a negative feedback modulator of ACh release. The clinical implications of these results are intriguing. Specifically, could specific adenosine receptor antagonists (e.g., 8-cyclopentyl-theophylline derivatives) maintain a high safety factor at the neuromuscular junction by preventing the normal depression of ACh release and thus alleviate the symptom of patients in disease states where skeletal muscle is readily fatigued (e.g. myasthenia gravis)?