The Senning lab focuses on the mechanisms of ion channel regulation in a class of sensory neurons known as nociceptors. The brain receives signals from the peripheral nervous system through the spinal cord. Some of these signals come in through the dorsal horn from DRG nociceptors, which extend processes out to the peripheral tissues, where molecular receptors act to change the excitability of the neuron. Because of its role in pain sensation, our research effort is directed at the function of TRPV1, which is a non-selective ion channel expressed in nociceptors. We consider three aspects of TRPV1 regulation and consequences to nociceptor excitability:

Nociceptors are modulated by a wide variety of sensory inputs. In the case of TRPV1 positive neurons, capsaicinoids, heat, acid and oxidation directly activate gating of TRPV1 to affect the excitability of the nociceptor. The poly-modal activation of TRPV1 beckons the question as to how such a broad set of inputs at near physiological levels can be integrated by the channel to modulate opening and closing.

Tissue inflammation results in the presences of an inflammatory soup that bathes the nociceptor in signaling molecules that influence the function of TRPV1 both directly (for example through acidity) or indirectly through signaling cascades. Both calcium and phosphatidylinositol 4,5-bisphosphate (PIP2) act as second messengers to influence the function of TRPV1, but the contentious issue is to what degree these act directly on the channel versus through indirect mechanisms such as channel phosphorylation.

The pseudo-unipolar character of the DRG nociceptor is evident given its branched axon and absence of any post-synaptic structures. This presents an interesting problem since an organizational polarity is lacking that would place TRPV1 at the periphery of the nociceptor. Our research is directed at identifying a mechanism that recruits TRPV1 to physiologically relevant sites.

• *Eric Senning and Andrew H. Marcus, “Actin Polymerization Driven Mitochondrial Transport in Mating S. cerevisiae,” Proc. Natl. Acad. Sci. USA 107, 721 (2010).
• *Eric N. Senning, Marcus D. Collins, Anastasiia Stratiievska, Carmen A. Ufret-Vincenty and Sharona E. Gordon, “Regulation of TRPV1 ion channel by phosphoinositide (4,5)-bisphosphate: the role of membrane asymmetry.” J. Biol. Chem. 289, 10999 (2014).
• *Eric N. Senning and Sharona E. Gordon, “Activity and Ca²⁺ regulate the mobility of TRPV1 channels in the plasma membrane of sensory neurons.” eLife 4, e03819 (2015). (http://dx.doi.org/10.7554/elife.03819)
• *Sharona E. Gordon, Eric N. Senning, Teresa K. Aman, and William N. Zagotta, “Transition metal ion FRET to measure short range distances at the intracellular surface of the plasma membrane.” J. Gen. Physiology 147, 189 (2016).
• *William N. Zagotta, Moshe T. Gordon, Eric N. Senning, Mika Munari, and Sharona E. Gordon, “Measuring distances between TRPV1 and the plasma membrane using a noncanonical amino acid and tmFRET.” J. Gen. Physiology 147, 201 (2016).
• *Anastasiia Stratiievska, Sara Nelson, Eric N. Senning, Jonathan D. Lautz, Stephen EP Smith, Sharona E. Gordon, “Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor,” eLife 2018;7:e38869; doi: (https://doi.org/10.7554/eLife.38869)
• Eric Senning, “With PIPs, you get ZIPs and blips,” J. Gen. Physiology 151, 971 (2019).

• “Optical Recording of Single-channel TRPV1 Activity and Mobility in Isolated Dorsal Root Ganglion (DRG) Neurons and Cultured Mammalian Cells,” platform presentation at the 57^th Annual Meeting of the Biophysical Society, Philadelphia, PA, February 2013
• “Optical Recording of Single-channel TRPV1 Activity in Intact Cells,” invited talk in the Biology Department seminar series of Western Washington University, Bellingham, WA, March 2014
• “Macromolecular Identity of an Ion Channel: How does TRPV1 do-si-do?,” invited talk in the Wagonner Center for Alcohol and Addiction Research at the University of Texas, Austin, TX, November 2017
• “TRPV1 by Fluorescence: Ion channel regulation in space and time,” invited talk in the Institute of Cell and Molecular Biology (ICMB) at the University of Texas, Austin, TX, March 2019
• “The unroofed cell: A native membrane experimental platform to study lipid-protein interactions,” invited talk at the Conference of Ion Channel Dynamics and Mechanisms in Austin, TX, November 2019.

Ion Channels: Molecular Physiology of Neuronal Signaling NEU 366C