Title

Regulation of intracellular calcium channels

Date of Completion

January 1996

Keywords

Biology, Cell|Biology, Animal Physiology

Degree

Ph.D.

Abstract

Two types of calcium (Ca) release channels have been identified in the endoplasmic/sarcoplasmic reticulum, the Ca-gated channel (ryanodine receptor, RyR) and the inositol 1,4,5-trisphosphate(InsP$\sb3$)-gated channel. Both types of channels are present in a wide range of tissues though the relative abundance varies. Calcium release from intracellular stores is important for a variety of cellular processes including muscle contraction, fertilization envelope formation and regulation of transcription. This dissertation examines the regulation of the intracellular Ca channels and explores the mechanisms through which regulation occurs. The activating effects of heparin on the RyR are presented in chapter 2. These studies demonstrate novel properties of a commonly used pharmacological tool. A mechanism for this activation is proposed and supported by experimental evidence. Chapter 3 discusses the regulation of RyR channels by an accessory protein. FKBP12 is shown to be necessary for normal RyR channel function. The final chapter discusses the regulation of InsP$\sb3$-gated channels by endogenous physiological modulators. The complex interaction between Ca and InsP$\sb3$ is examined and a model is proposed that describes how these regulators affect channel activity. ^

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