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

膜片钳电生理学是塞纳托雷博士研究计划的核心部分。他和他的团队继续研究神经交流和神经系统进化的分子基础。他是校园里唯一拥有在单细胞水平上研究离子通道和神经递质受体结构和功能的电生理学系统的研究人员。这个可用的系统可以记录哺乳动物细胞系中表达的离子通道和神经递质受体的膜电流，并在记录的细胞上灌流不同的溶液，用于研究药理学、离子选择性和配体激活。 最近，共同申请者Voula Kanelis博士开始与Senatore博士合作开展电生理学研究，她试图扩大对ATP激活的钾通道结构和功能特性的研究，该通道在心血管系统健康和疾病中非常重要。 现有的电生理学系统需求量极大，HQP正在努力完成他们的实验。Senatore和他的人员共享一个系统来研究在神经突触通信中扮演重要角色的23种不同的离子通道，包括检测分泌的质子和神经肽的Deg/ENaC钠通道受体，检测分泌的谷氨酸和甘氨酸的谷氨酸受体，以及在神经递质释放和突触信号中发挥核心作用的电压门控钙通道。 在他担任首席研究员的头五年里，塞纳托雷博士和他的团队使用这个单一的电生理学系统取得了一些令人兴奋的发现，这些发现将继续产生影响巨大的出版物，并对他的领域做出重大贡献。然而，由于需求很高，他的HQP在利用他们的研究机会方面面临着巨大的挑战。目前，塞纳托雷博士的研究生们轮流工作，通常是在午夜以后，以便有足够的时间进行研究。他们对自己开展工作的能力表示严重关切。这不是一个短期问题，他的研究将继续主要依靠电生理学。卡内利斯博士和她的HQP还需要经常接触电生理系统。 因此，正在申请资金购买第二个电生理学系统，这将缓解研究瓶颈，并提供扩展的电流钳记录能力。电流钳记录很重要，因为研究人员可以用它来表征细胞的电特性，这些细胞天然地表达正在研究的各种离子通道和神经递质受体。 NSERC RTI是申请者能够获得足够资金购买这一关键基础设施的唯一手段。然而，如果这项申请成功，塞纳托雷博士将从他的个人资金中拿出2万美元用于购买。

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.