Student Theses and Dissertations
Date of Award
1967
Document Type
Thesis
Degree Name
Doctor of Philosophy (PhD)
Thesis Advisor
Clarence Connelly
Keywords
voltage clamp, myelinated nerve fibers, sodium ion channels, potassium ion channels, drug effects, ion permeability
Abstract
The effects of various drugs on single myelinated nerve fibers from Rana pipiens were studied with the voltage clamp technique of Frankenhaeuser and Dodge. The observed currents were analysed by a computer in terms of the mathematical model of Hodgkin and Huxley. The sodium, the potassium, and the leakage current components and the time constants associated with their changes were calculated. Tetrodotoxin abolished the sodium currents selectively, and tetraethylammonium ion abolished the potassium currents selectively. Neither of these drugs affected the time constants associated with any of the current components. The curves relating the kinetic parameters of the sodium currents to the voltage were displaced along the voltage axis by calcium concentration changes. The three agents mentioned acted rapidly (within one second) and reversibly and probably bind to specific receptors on the extracellular side of the nodal membrane. Other drugs including local anesthetics, some general anesthetics, and veratrine alkaloids exerted moderately specific effects on the components of current. The anesthetics abolished sodium currents and the veratrine alkaloids enhanced sodium currents and prolonged their time courses. None of the agents tested affected the leakage current. The demonstrated pharmacological independence of the three components of current suggests that the ion fluxes are handled by independent permeability systems, the sodium channels, the potassium channels, and the leakage channels. Some of the properties of these channels are described.
License and Reuse Information
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Recommended Citation
Hille, Bertil, "A Pharmacological Analysis of the Ionic Channels of Nerve" (1967). Student Theses and Dissertations. 569.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/569
Comments
A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy