Initiation, Maintenance, and Termination of Bursting in an Endogenously Bursting Molluscan Nerve Cell (cyclic-Amp)

This thesis deals with initiation, maintenance and termination of bursting in an endogenously bursting nerve cell. The ventral white cells (VWC) of the marine mollusc Pleurobranchaea californica become endogenous bursters when the intracellular levels of cyclic 3'5' adenosine monophosphate (cAMP) are raised. cAMP increases the opening frequency of membrane sodium iontophores eliciting an inward current which depolarizes the VWC and leads to action potential bursting and broadening. The opening frequency is not voltage-dependent, but is sensitive to the voltage-dependent accumulation of intracellular calcium ions. Injection of cAMP at various holding potentials shows that peak current is maximal in the voltage region (-40 to -20 mV) that supports bursting and calcium influx. Removal of extracellular calcium eliminates this voltage effect, indicating the potentiating role of calcium. Extracellular calcium has a direct effect on conductance; increasing calcium decreases conductance via competition for a binding site. The cAMP-stimulated inward current has a characteristic waveform. Inhibition of various components of the cAMP machinery induces unique changes in the shape of the cAMP-stimulated inward current waveform. Inhibition of phosphodiesterase (PDE; the degradative enzyme for cAMP) increases the peak amplitude. Protein kinase and phosphatase decrease and increase, respectively, the peak amplitude, but neither significantly changes the duration. Mathematical modeling of the major enzymatic steps elicited by cAMP injection verifies that the change in waveform is indicative of the locus of the change. Changing the intracellular pH (pH(,i)) in either direction from resting pH(,i) (7.4), and inhibition of calmodulin, increases inward current. Depolarizing pulses in the presence of extracellular calcium reduces inward current. The changes in current waveform by pH(,i) changes, calmodulin inhibition, and depolarization are all consistent with changes in PDE activity. This indicates that the calcium/calmodulin-stimulated PDE is a critical site for enzyme regulation. A model is proposed whereby a complex interaction of pH(,i) and calcium modify the cAMP-stimulated inward current through PDE. This elucidates a novel mechanism wherein PDE regulates burst maintenance and termination, as well as the overall responsiveness of the neuron to cAMP.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Green, Daniel Joseph

• Biology, Neuroscience

Language dc:language

eng

Identifier

(UMI)AAI8600197

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/77680