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oai:www.ideals.illinois.edu:2142/21576 2023-07-10 col_2142_5131 col_2142_16508 com_2142_5130 com_2142_16507 com_2142_14793 com_2142_8903

Huang, Rong-Chi 2011-05-07T13:12:44Z 2011-05-07T13:12:44Z 10000-01-01 1989 Effects of cyclic AMP on pedal neurons of the marine mollusc, Pleurobranchaea californica were studied by intracellular iontophoresis of cyclic AMP under voltage clamp condition. The I$\sb{\rm Na,cAMP}$ response to cyclic AMP injection is resistant to protein kinase inhibitors, and is very likely mediated by direct cyclic AMP binding to the channel receptor. The slow I$\sb{\rm Na,cAMP}$ is regulated by diffusion-hydrolysis kinetics: it varied in latency to current onset, latency to peak amplitude, and amplitude with the distance of the membrane to the tip of the iontophoretic cyclic AMP injection electrode; the phosphodiesterase inhibitor isobutylmethyxanthine (IBMX) in increasing concentrations motonically decreased the decay rates of the I$\sb{\rm Na,cAMP}$ response. A diffusion-reaction model incorporating terms for diffusion and degradation of cyclic AMP accurately fitted the time course of I$\sb{\rm Na,cAMP}$ response to a pulse of cyclic AMP. An application of the model allows extraction of phosphodiesterase activity as a first-order rate constant from the exponential decay phase of the I$\sb{\rm Na,cAMP}$ response. Intracellular Ca$\sp{2+}$ suppresses the I$\sb{\rm Na,cAMP}$ response; in contrast, serotonin, IBMX, and tonic injection of cyclic AMP tonically activate the I$\sb{\rm Na,cAMP}$ response and reduce its sensitivity to Ca$\sp{2+}$ modulation. The mutually antagonistic effects of intracellular Ca$\sp{2+}$ and cyclic AMP on the I$\sb{\rm Na,cAMP}$ response were best explained in terms of a competitive binding model: intracellular Ca$\sp{2+}$ suppresses I$\sb{\rm Na,cAMP}$ by decreasing the channel binding for cyclic AMP, and cyclic AMP decreases the channel affinity for intracellular Ca$\sp{2+}$. The competitive binding model also predicts supporting results of experiment tests. Extracellular Ca$\sp{2+}$ also regulates I$\sb{\rm Na,cAMP}$ by affecting cyclic AMP binding affinity in addition to its effect on channel conductance. Low extracellular Ca$\sp{2+}$ converts a low maximum amplitude/high cyclic AMP binding affinity current to a high maximum amplitude/low cyclic AMP binding affinity one; this design augments the intracellular Ca$\sp{2+}$ suppressive effect and thus serves as a safeguard preventing high cyclic AMP-induced pathological excitation. In conclusion, low extracellular Ca$\sp{2+}$ complements intracellular Ca$\sp{2+}$ in regulating I$\sb{\rm Na,cAMP}$ response. Made available in DSpace on 2011-05-07T13:12:44Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9010897.pdf: 6089267 bytes, checksum: c2f5cd2ca325d22d2a0f4fc8ec78ce2a (MD5) Previous issue date: 1989 Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:51:43Z Item is restricted indefinitely. Restriction data tranferred 2014-07-01T11:23:46-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission ETDs are only available to UIUC Users without author permission U of I Only AAI9010897 (UMI)AAI9010897 http://hdl.handle.net/2142/21576 eng Copyright 1989 Huang, Rong-Chi Biology, Neuroscience Biology, Animal Physiology The cyclic AMP-activated sodium current in the molluscan neuron: A kinetic analysis of regulation by diffusion, phosphodiesterase and calcium ion text Molecular and Integrative Physiology Physiology University of Illinois at Urbana-Champaign Dissertation Ph.D.