Graduation Year

2008

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Physics

Major Professor

Wei Chen, Ph.D.

Keywords

Channel, Pump, Synchronization, Modulation, Kidney

Abstract

The most important and most common channels on cell membrane are voltage-gated Na+ and K+ channels. In so-called "excitable cells" like neurons and muscle cells, these channels open or close in response to changes in potential across the membrane in order to accomplish muscle contraction and transmit signals. By controlling the membrane potential, we observe extraordinary inactivation behaviors of the voltage-gated Na+ channels and the voltage-gated delayed rectifier K+ channels, which shows that electric stimulation pulses can temporarily close the Na+ and K+ channels, just as drugs, like tetrodotoxin (TTX) and tetraethylammonium (ETA), do. The Na/K pump is essential for living system and is expressed in virtually all cell membranes.

The ionic transport conducted by Na/K pumps creates both an electrical and a chemical gradient across the plasma membrane, which are required for maintaining membrane potentials, cell volume, and secondary active transport of other solutes, etc. We use a pulsed, symmetric, oscillating membrane potential with a frequency close to the mean physiological turnover rate across the cell membrane to synchronize Na/K pump molecules. The pump molecules can work as a group, pumping at a synchronized pace after a long train of pulses. As a result, the pump functions can be significantly increased. After the pump molecules are synchronized, the applied electric-field frequency can gradually increase in order to resynchronize the molecules to a new, higher frequency. Modulating the pump molecules to a higher frequency leads to a significant increase of pump current. Synchronization and modulation of pump molecules can become a new method to study the function of Na/K pump molecules.

This method has huge potential applications in clinic medical treatment. After single-fiber-level study, the final project is on organ level, the rat kidney, by using synchronization and modulation of Na/K pump molecules on the proximal tubule membrane. Because Na+ re-absorption is directly related to the function of the Na/K pump, the more active Na/K pumps are, the more Na+ ions can be absorbed, which results in an increased potential inside the renal proximal tubule. This project is the first step of synchronization and modulation applied on the level of an organ.

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