Cyclic nucleotide-gated ion currents are a large family whose functions range from sensory transduction to pattern generation in members of neural networks. Our broad research objective is to understand the function of one such current, INa,CAMP, in a central nervous system context. In central neurons, Ina,CAMP is regulated in a complex fashion by CAMP, multiple actions of Ca2+, intracellular Ph, and voltage; these factors confer sensitivity to neural activity and shape the current's contributions to neuronal pattern generation. The mollusc Pleurobranchaea provides a well-developed model system of large and well characterized neurons in which Ina,CAMP is expressed in a neuromodulatory framework. These neurons permit straightforward patch and voltage clamp recordings of Ina,CAMP in combination with a variety of experimental manipulations. This proposal describes a plan to elucidate mechanisms of channel regulation and the neuromodulatory context of function. Proceeding from previous work, we are pursuing three specific goals: 1) elucidation of mechanisms of potentiation an inactivation by intracellular Ca2+, current suppression by extracellular Ca2+, and potentiation by H+; 2) probing mechanisms of voltage-dependence of the current; and 3) describing the neuromodulatory context within which Ina, CAMP acts. The first two goals will be approached in studies of inside- out and cell-intact patch recordings of single channel activity, in combination with manipulations of cofactors and inorganic ions. The third goal will be sought in voltage clamp studies of serotonergic neuromodulation of Ina,CAMP using the ion current to report on CAMP metabolism. Ina,CAMP appears to have prominent roles in mediating aspects of behavioral arousal and effects of convulsant drugs. The likely broad distribution of this type of ion current and its combinatorial regulation lends it relevance to many aspects of neural plasticity, pattern generation, and dysfunction in brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS026838-06
Application #
2266147
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1990-01-01
Project End
1997-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
6
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Potgieter, Kurt; Hatcher, Nathan G; Gillette, Rhanor et al. (2010) Nitric oxide potentiates cAMP-gated cation current by intracellular acidification in feeding neurons of pleurobranchaea. J Neurophysiol 104:742-5
Hatcher, Nathan G; Sudlow, Leland C; Moroz, Leonid L et al. (2006) Nitric oxide potentiates cAMP-gated cation current in feeding neurons of Pleurobranchaea californica independent of cAMP and cGMP signaling pathways. J Neurophysiol 95:3219-27
Jing, J; Gillette, R (1999) Central pattern generator for escape swimming in the notaspid sea slug Pleurobranchaea californica. J Neurophysiol 81:654-67
Sudlow, L C; Jing, J; Moroz, L L et al. (1998) Serotonin immunoreactivity in the central nervous system of the marine molluscs Pleurobranchaea californica and Tritonia diomedea. J Comp Neurol 395:466-80
Floyd, P D; Moroz, L L; Gillette, R et al. (1998) Capillary electrophoresis analysis of nitric oxide synthase related metabolites in single identified neurons. Anal Chem 70:2243-7
Moroz, L L; Sudlow, L C; Jing, J et al. (1997) Serotonin-immunoreactivity in peripheral tissues of the opisthobranch molluscs Pleurobranchaea californica and Tritonia diomedea. J Comp Neurol 382:176-88
Sudlow, L C; Gillette, R (1997) Cyclic AMP levels, adenylyl cyclase activity, and their stimulation by serotonin quantified in intact neurons. J Gen Physiol 110:243-55
Cruz, L; Moroz, L L; Gillette, R et al. (1997) Nitrite and nitrate levels in individual molluscan neurons: single-cell capillary electrophoresis analysis. J Neurochem 69:110-5
Moroz, L L; Gillette, R (1996) NADPH-diaphorase localization in the CNS and peripheral tissues of the predatory sea-slug Pleurobranchaea californica. J Comp Neurol 367:607-22
Moroz, L L; Chen, D; Gillette, M U et al. (1996) Nitric oxide synthase activity in the molluscan CNS. J Neurochem 66:873-6

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