Electrophysiology system for comparative structure-function studies of ion channels and neurotransmitter receptors

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Patch-clamp electrophysiology is a core part of Dr. Senatore's research program. He and his team pursue questions on the molecular underpinnings of neural communication, and nervous system evolution. He is the only researcher on campus with an electrophysiology system for studying ion channel and neurotransmitter receptor structure and function at the single cell level. This available system permits recording of membrane currents of ion channels and neurotransmitter receptors expressed in mammalian cell lines, and to perfuse different solutions over recorded cells for studying pharmacology, ion selectivity and ligand activation. Recently, the co-applicant Dr. Voula Kanelis began collaborating with Dr. Senatore to carry out electrophysiology studies, as she seeks to expand her research into the structure-function properties of ATP-activated potassium channels, important in cardiovascular system health and disease. The available electrophysiology system is in extremely high demand, and HQP are struggling to complete their experiments. Senatore and his personnel share the single system to study 23 different ion channels with important roles in neural synaptic communication, including Deg/ENaC sodium channel receptors that detect secreted protons and neuropeptides, glutamate receptors that detect secreted glutamate and glycine, and voltage-gated calcium channels that play central roles in neurotransmitter release and synaptic signaling. Over his first five years as a principal investigator, Dr. Senatore and his team have used this single electrophysiology system to make some exciting discoveries that will continue to yield high impact publications and make significant contributions to his field. However, due to the high demand, his HQP are experiencing significant challenges in capitalizing on their research opportunities. Currently, Dr. Senatore's graduate students are working in shifts, often past midnight, in order to have enough time to do their research. They have expressed serious concerns about their ability to conduct their work. This is not a short term problem, and his research will continue to rely centrally on electrophysiology. Dr. Kanelis and her HQP also need frequent access to an electrophysiology system. Thus, funds are being requested to purchase a second electrophysiology system which will relieve the research bottleneck, plus provide the extended capability of current-clamp recording. Current-clamp recording is important as the researchers can use it to characterize the electrical properties of cells that natively express the various ion channels and neurotransmitter receptors being studied. NSERC RTI is the only means by which the applicants can acquire enough funds to purchase this crucial piece of infrastructure. However, Dr. Senatore will contribute $20,000 of his personal funds towards the purchase, should this application be successful.