The synapse is a specialized junction for communication between neurons. Synapses can also occur between cells of the immune system. My research is focused on the function of the presynaptic component of synapses in nerve and immune tissues, and in particular, the role of ion channels and Ca²⁺ signaling in regulating presynaptic excitability. These studies utilize electrophysiological (patch-clamp), cell fluorescence and biochemical techniques.

Noxious stimuli (mechanical, thermal or chemical) activate specific ion channels in sensory nerve endings, thereby generating action potentials that propagate to the spinal cord and brain. One of these channels, the capsaicin (or vanilloid) receptor, is found in sensory c-fibers and plays a critical role in thermal and inflammatory pain signaling. Several types of voltage-dependent Na⁺ channels also play important roles in action potential propagation to central terminals. A goal of this study is to understand the regulation of these channels and how they contribute to pain transmission at peripheral and central nerve terminals.

The synapse between a "dendritic" (antigen-presenting) cell, and a T cell, represents the cradle of acquired immunity. Here the dendritic cell instructs a naïve T cell to initiate (or terminate) an immune response. A major goal of this research is to understand how ion channels and Ca²⁺ signaling pathways in the dendritic cell contribute to the functioning of this unusual synapse.

Selected Publications:

• Cornett PM, Matta JA, Ahern GP  General anesthetics sensitize the capsaicin receptor transient receptor potential V1.  Mol Pharmacol. 74:1261-1268, 2008

• Matta JA, Cornett PM, Miyares RL, Abe K, Sahibzada N, Ahern GP  General anesthetics activate a nociceptive ion channel to enhance pain and inflammation.  Proc Natl Acad Sci USA 105:8784-8789, 2008

• Motter AL, Ahern GP  TRPV1-null mice are protected from diet-induced obesity.  FEBS Lett.  582:2257-2262, 2008

• Matta JA, Ahern GP: Voltage is a partial activator of rat thermosensitive TRP channels. J Physiol. 585:469-82, 2007

• Franco R, Pacheco R, Lluis C, Ahern GP, O'Connell PJ: The emergence of neurotransmitters as immune modulators. Trends Immunol. 28:400-7, 2007

• Pingle SC, Matta JA, Ahern GP: Capsaicin receptor: TRPV1 a promiscuous TRP channel. Handb Exp Pharmacol. 179:155-71, 2007

• León-Ponte M, Ahern GP, O'Connell PJ: Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor. Blood. 109:3139-46, 2007

• Matta JA, Miyares RL, Ahern GP: TRPV1 is a novel target for omega-3 polyunsaturated fatty acids. J Physiol. 578:397-411, 2007

• Stolk M, Leon-Ponte M, Merrill M, Ahern GP, O'Connell PJ: IP3Rs are sufficient for dendritic cell Ca2+ signaling in the absence of RyR1. J Leukoc Biol. 80:651-8, 2006

• Ahern GP, Wang X, Miyares RL: Polyamines are potent ligands for the capsaicin receptor TRPV1. J Biol Chem. 281:8991-5, 2006

• O'Connell PJ, Wang X, Leon-Ponte M, Griffiths C, Pingle SC, Ahern GP: A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells. Blood. 107:1010-7, 2006

• O'Connell PJ, Pingle SC, Ahern GP: Dendritic cells do not transduce inflammatory stimuli via the capsaicin receptor TRPV1. FEBS Lett. 579:5135-9, 2005

• Ahern GP, Brooks IM, Miyares RL, Wang XB: Extracellular cations sensitize and gate capsaicin receptor TRPV1 modulating pain signaling. J Neurosci. 25:5109-16, 2005

• Wang X, Miyares RL, Ahern GP: Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and reduces short-term food intake in mice via capsaicin receptor TRPV1. J Physiol. 564:541-7, 2005

• Ahern GP: Activation of TRPV1 by the satiety factor oleoylethanolamide. J Biol Chem. 278:30429-34, 2003

• Ahern GP, Premkumar LS: Voltage-dependent priming of rat vanilloid receptor: effects of agonist and protein kinase C activation. J Physiol. 545:441-51, 2002

• Ahern GP, Klyachko VA, Jackson MB: cGMP and S-nitrosylation: two routes for modulation of neuronal excitability by NO. Trends Neurosci. 25:510-7, 2002

• O'Connell PJ, Klyachko VA, Ahern GP: Identification of functional type 1 ryanodine receptors in mouse dendritic cells. FEBS Lett. 512:67-70, 2002

• Klyachko VA, Ahern GP, Jackson MB: cGMP-mediated facilitation in nerve terminals by enhancement of the spike after-hyperpolarization. Neuron. 31:1015-25, 2001

• Hsu Sf, O'Connell PJ, Klyachko VA, Badminton MN, Thomson AW, Jackson MB, Clapham DE, Ahern GP: Fundamental Ca2+ signaling mechanisms in mouse dendritic cells: CRAC is the major Ca2+ entry pathway. J Immunol. 166:6126-33, 2001

• Premkumar LS, Ahern GP: Induction of vanilloid receptor channel activity by protein kinase C. Nature. 408:985-90, 2000

• Ahern GP, Hsu SF, Klyachko VA, Jackson MB: Induction of persistent sodium current by exogenous and endogenous nitric oxide. J Biol Chem. 275:28810-5, 2000

• Hsu SF, Ahern GP, Jackson MB: Ultra-violet light-induced changes in membrane properties in secretory cells. J Neurosci Methods. 90:67-79, 1999