In the human brain, there are approximately 100 billion neurons that make an even larger number of synaptic connections. Collectively, these intricate connections create the neural circuits that form the basis of complex behaviors, underlying our emotions, our actions, our thinking. A major focus of neuroscience research is to understand the function of these neural circuits in both normal and diseased states. Neurons communicate with each other using a combination of tiny electrical and chemical signals. Our laboratory studies the function of small proteins, known as 'ion channels', that are essential for controlling these electrical signals in the brain. A large number of human diseases have been linked to mutations in ion channels, so called channelopathies. Our research focuses on the function of potassium ion channels, which control the flow of potassium ions across the cell membrane and generate one of the most important inhibitory signals in the brain.
The appropriate balance and timing of excitatory and inhibitory signals are critical for the normal function of neural circuits in the brain. Research in the Slesinger laboratory focuses on a fundamental pathway for inhibition in the brain that is mediated by G protein-coupled receptors (GPCR) and G protein-gated inwardly rectifying potassium channels (referred to as 'GIRK' channels). Many neurotransmitters in the brain activate GPCRs which in turn opens GIRK channels. Previous work in the lab has established that GIRK channels exist in a macromolecular signaling complex that incorporates the channel, G proteins, receptors and regulator proteins into a microdomain. We identifed the first regulator of GIRK channel trafficking, SNX27, and demonstrated that alcohol interacts directly with a physical pocket in GIRK channels. The long-term goal of our research is to elucidate the function of GIRK channels in the brain, with a particular emphasis on their role in drug addiction and therapeutic potential. Currently, there are several different projects in the laboratory that range from molecular studies of GIRK channel function to identifying key pathways and proteins altered in human's addicted to psychostimulants.
|Paul Slesinger, PhD|
|Sorting nexin 27 regulation of G protein-gated inwardly rectifying K+ channels attenuates in vivo cocaine response. Munoz MB, Slesinger PA., Neuron. 2014 May 7;82(3):659-69. doi: 10.1016/j.neuron.2014.03.011.|
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