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Paul A. Slesinger

 

Paul A. Slesinger

Paul A. Slesinger

Associate Professor
Clayton Foundation Laboratories for Peptide Biology

"Drugs of abuse can produce long-term changes in the electrical activity of neurons in the brain. Recently, we have been researching a new role for Girk potassium channels—proteins that control the movement of potassium ions in the brain—in drug addiction. Our studies may provide new insights into the cellular mechanisms of drug addiction as well as some mental disorders, such as schizophrenia and attention deficit hyperactivity disorder (ADHD)."

Our brains are constantly buzzing with tiny electrical signals that enable neurons to "talk" to each other. This electrical activity is created by sodium and potassium ions moving in and out of neurons through specialized holes, called ion channels. Girk channels—a subtype of many different potassium channels in the brain—are widely distributed in the brain and regulate neuron-toneuron communication. In response to incoming signals, these Girk channels open up, creating many little "potassium leaks," and as a result the signals fizzle.

To prevent the constant chatter from descending into chaos, the activity of these ion channels has to be tightly regulated. Slesinger and his team have been searching for ways to control the levels of Girk channels in the brain. Recently, he discovered that a small, relatively unknown protein called Snx27 associates directly with the Girk channels. Further studies showed that Snx27 functions like an intracellular traffic coordinator, pulling potassium channels from the front-line and whisking them to a cellular plant for disposal.

Interestingly, the levels of Snx27 increase in response to drugs of abuse, such as the psychostimulants methamphetamine and cocaine. Previous work by Slesinger and his colleagues also revealed a unique role for Girk channels in addiction. These new findings have prompted Slesinger to ask whether changes in the expression of Snx27 provide an important link between the shuffling of Girk channels and the addictive properties of psychostimulants in the brain.

Slesinger and his team are now testing these ideas using animal models of drug addiction. Mice injected repetitively with methamphetamine for five days become extremely hyperactive in response to the drug. This heightened response remains even after two weeks of abstinence, suggesting a long-term effect of the abused drug. The Slesinger lab is now examining these mice for changes in Snx27 and Girk signaling and assessing their role in mediating the long-term effects of addictive drugs. Their work may unravel new therapeutic pathways for treating drug addictions.

Lab Photo

Left to right:
Top/In tree: Paul Slesinger Back row: Bartosz Balana, Laia Bahima, Michelle Lee, Stephanie Boyer, Victory Joseph, Dave Dalton Sitting: Claire Padgett, Prafulla Aryal, Debbie Doan, Natalie Taylor, Michaelanne Munoz

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Paul A. Slesinger

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Paul A. Slesinger

Paul A. Slesinger

Associate Professor
Clayton Foundation Laboratories for Peptide Biology

Nerve cells communicate by sending electrical impulses along their axons, long, hair-like extensions that reach out to neighboring nerve cells. These impulses involve the opening and closing of ion channels and allow ions – electrically charged atoms – or small molecules to enter or leave the cell. The flow of these ions creates an electrical current that produces tiny voltage changes across the membrane. In his quest to understand how brain cells communicate, Dr. Paul A. Slesinger, Associate professor in the Clayton Foundation Laboratories for Peptide Biology, focuses on one particular type of channel that allows potassium ions to cross the cell membrane.

Slesinger's research ranges from studies on the molecular details of how potassium ion channels open and close to a cellular level on the role potassium channels have in nerve cell signaling. Recent studies in the lab have also turned to investigating the role of potassium channels in drug addictions and mental disorders. Drugs can significantly alter the actions of nerve cell receptors and channels. Slesinger and his team are now looking at how to selectively manipulate the receptors and/or channels and at the cell signaling pathways that lead to addictions. They are also studying other parts of the brain, where these receptors and potassium channels may play a role in memory and other mental functions.

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