The Laboratory of Molecular Physiology was established in February of 2002 and moved into renovated laboratory space in March of 2002. The Section on Transmitter Signaling was inaugurated at this time. The primary focus of the section is to further our understanding of the molecular basis of signaling between G protein coupled receptors and voltage gated ion channels in neurons using electrophysiological, molecular, and imaging techniques. Dr. Paul Kammermeier, joined the Section in February 2002 as research fellow. Dr Huanmian Chen joined the Section in March of 2002 as a postdoctoral IRTA followed by Drs. Henry Puhl and Juan Guo as Staff Scientist and Visiting Fellow, respectively, in August 2002. Subsequently, Dr. Kammermeier, accepted an Assistant Professor position at the Northeast Ohio Universities College of Medicine and departed in late August of 2002. Dr. John Partridge will join the section in October of 2002 as a research fellow thereby completing the staff of the Section on Transmitter Signaling. Active recruitment for a Section Chief of the Imaging Section is currently underway with plans for establishment of the section projected for late 2002 or early 2003. Laboratory space has recently been renovated to house the Imaging Section. Projects currently getting started include investigation of the signaling components underlying modulation of calcium channels in peripheral and central neurons. The use of small interfering RNA (siRNA) to ablate specific genes is being evaluated in neurons using microinjection techniques. Preliminary data suggest that the technique will be useful for targeting precise components of the signaling pathways that link receptors with ion channels. A second project aims to establish whether G proteins influence the agonist pharmacology of CB1 cannabinoid receptors. In particular, the ability of G protein alpha subunit to dictate efficacy of naturally occurring endocannabinods will be examined. Finally, new optical techniques are being developed to facilitate real time monitoring of receptors, signaling molecules and ion channels in neurons. A microscopy system designed to utilize a combination of Total Internal Reflectance Fluorescence (TIRF) and Fluorescence Resonance Energy Transfer (FRET) is under construction and the potential of this instrument to probe neuronal protein-protein interactions on a millisecond time scale will be evaluated.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Intramural Research (Z01)
Project #
1Z01AA000430-01
Application #
6674348
Study Section
(LMP)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Thaler, Christopher; Koushik, Srinagesh V; Puhl 3rd, Henry L et al. (2009) Structural rearrangement of CaMKIIalpha catalytic domains encodes activation. Proc Natl Acad Sci U S A 106:6369-74
Guo, Juan; Williams, Damian J; Ikeda, Stephen R (2008) N-arachidonoyl L-serine, a putative endocannabinoid, alters the activation of N-type Ca2+ channels in sympathetic neurons. J Neurophysiol 100:1147-51
Schofield, Geoffrey G; Puhl 3rd, Henry L; Ikeda, Stephen R (2008) Properties of wild-type and fluorescent protein-tagged mouse tetrodotoxin-resistant sodium channel (Na V 1.8) heterologously expressed in rat sympathetic neurons. J Neurophysiol 99:1917-27
Puhl 3rd, Henry L; Ikeda, Stephen R (2008) Identification of the sensory neuron specific regulatory region for the mouse gene encoding the voltage-gated sodium channel NaV1.8. J Neurochem 106:1209-24
Guo, Juan; Williams, Damian J; Puhl 3rd, Henry L et al. (2008) Inhibition of N-type calcium channels by activation of GPR35, an orphan receptor, heterologously expressed in rat sympathetic neurons. J Pharmacol Exp Ther 324:342-51
Chen, Huanmian; Puhl 3rd, Henry L; Ikeda, Stephen R (2007) Estimating protein-protein interaction affinity in living cells using quantitative Forster resonance energy transfer measurements. J Biomed Opt 12:054011
Ikeda, Stephen R; Dunlap, Kathleen (2007) Calcium channels diversify their signaling portfolio. Nat Neurosci 10:269-71
Yang, Qing; Sumner, Andrew D; Puhl, Henry L et al. (2006) M(1) and M(2) muscarinic acetylcholine receptor subtypes mediate Ca(2+) channel current inhibition in rat sympathetic stellate ganglion neurons. J Neurophysiol 96:2479-87
Koushik, Srinagesh V; Chen, Huanmian; Thaler, Christopher et al. (2006) Cerulean, Venus, and VenusY67C FRET reference standards. Biophys J 91:L99-L101
Guo, Juan; Chen, Huanmian; Puhl 3rd, Henry L et al. (2006) Fluorophore-assisted light inactivation produces both targeted and collateral effects on N-type calcium channel modulation in rat sympathetic neurons. J Physiol 576:477-92

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