Date of Award:

5-1-2003

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Biology

Committee Chair(s)

Brett A. Adams

Committee

Brett A. Adams

Committee

Daryll B. DeWald

Committee

Scott A. Ensign

Committee

Timothy A. Gilbertson

Committee

Jon Y. Takemoto

Abstract

Ca2+ entry through voltage-gated Ca2+ channels contributes to the regulation of neuronal membrane excitability, neurosecretion, and gene expression. The nervous system regulates these physiological processes through G protein-coupled receptors (GPCRs), which strongly modulate Ca2+ channel activity. This dissertation provides significant new information concerning modulation of neuronal L-, N,- and R-type Ca2+ channels by muscarinic acetylcholine receptors. The major findings of this work are: 1) CaV2.3 channels are differentially modulated by Gαq-coupled muscarinic receptors; 2) reconstituted slow muscarinic inhibition of CaV1.2c can be triggered by either M1, M3, or M5 muscarinic receptors; 3) the amino-terminus of Regulator of G protein signaling 2 (RGS2) targets RGS2 to the slow muscarinic cascade; 4) Activator of G protein signaling-1 (AGS-1) promotes tonic voltage-dependent inhibition of CaV2.2. My findings suggest that RGS proteins and AGS-1 may exert both acute and long-lasting effects on neuronal function by regulating Ca2+ influx through neuronal Ca2+ channels.

Included in

Biology Commons

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