Properties of the first genetically engineered neuron.

Citation

Hsu, Hsiaolan S. (1993) Properties of the first genetically engineered neuron. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/svss-ye57. https://resolver.caltech.edu/CaltechTHESIS:12062012-091333466

Abstract

Electrically excitable channels were expressed in Chinese hamster ovary cells using a vaccinia virus vector system. In cells expressing rat brain IIA Na^+ channels, brief pulses (< 1ms) of depolarizing current resulted in action potentials with a prolonged (0.5-3s) depolarizing plateau; this plateau was caused by slow and incomplete Na^+ channel inactivation. In cells expressing both Na^+ and Drosophila Shaker H4 transient K^+ channels, there were neuron-like action potentials. In cells with appropriate Na^+/K^+ current ratios, maintained stimulation produced repetitive firing over a 10-fold range of frequencies but eventually led to "lockup" of the potential at a positive value after several seconds of stimulation; the latter effect was due primarily to slow inactivation of the K^+ currents. Numerical simulations of modified Hodgkin-Huxley equations describing these currents, using parameters from voltage-clamp kinetics studied in the same cells, accounted for most features of the voltage trajectories. The present study shows that insights into the mechanisms for generating action potentials and trains of action potentials in real excitable cells can be obtained from the analysis of synthetic excitable cells that express a controlled repertoire of ion channels. This model system provides a direct control of complexity of neuronal behavior, and a tool for studying various forms of neural modulation at molecular and cellular levels.

Thesis Files