Student Theses and Dissertations
Date of Award
1963
Document Type
Thesis
Degree Name
Doctor of Philosophy (PhD)
Thesis Advisor
Clarence Connelly
Keywords
frogs, ion permeability, voltage clamp, action potential, sodium and potassium currents, myelinated nerve fibers
Abstract
Investigations by Huxley and Stämpfli of the dependence of the resting potential and of the action potential at the node of Ranvier upon the ionic composition of the bathing medium provided evidence that the electrical activity resulted from a sequential alteration of the membrane permeability to sodium and to potassium ions. Their results suggested that the nodal membrane conformed in a general way to the ionic hypothesis developed in detail for the squid axon by Hodgkin and Huxley. This dissertation reports an investigation of the electrical characteristics of the nodal membrane aimed at developing a quantitative formulation of the ionic hypothesis applicable to the node. Electronic control systems developed by Frankenhaeuser were used to measure the electrical responses of the node under the condition that either the membrane current or the potential difference across the nodal membrane was the controlled variable. Constraint of the membrane current provided accurate measurement of the action potential and related phenomena typical of nerve excitation. Constraint of the membrane potential (the voltage clamp) provided direct measurement of the current carried by the movement of ions through the membrane. By applying operational procedures analogous to those used by Hodgkin and Huxley for the squid axon, the ionic current was resolved into components carried specifically by sodium and by potassium ions. Measurements of the relations between the specific ionic currents and their electrochemical driving forces were used to define appropriate quantitative measures of the specific sodium and potassium permeabilities. Critical examination of the kinetics of the permeability changes showed that the rate constants governing the variation of the permeabilities depend only upon the membrane potential and not upon the current or time. The kinetics are accurately described by empirical equations of the same form as those developed by Hodgkin and Huxley for the squid axon. These empirical rate equations, together with the theoretical equations defining the specific ionic permeabilities and the theoretical equation for the distribution of current along the fiber, constitute an essentially complete mathematical model of the myelinated nerve fiber. Numerical solutions of these equations, under the appropriate boundary conditions, have established that the ionic hypothesis provides a sufficient and consistent interpretation of the action potential, subthreshold response, impedance change during an action potential, ionic exchanges during activity, refractoriness, and other phenomena as sociated with excitation and with conduction of the action potential. Good agreement between the theoretical computations and the experimental observations has established the validity of the voltage-clamp analysis such that this may be confidently extended to characterize further the properties of the nodal membrane. In preliminary experiments aimed at elucidating the nature of the ionic selectivity of the membrane, it was found that during the state of high sodium permeability the membrane is only partially selective against ammonium ions.
License and Reuse Information
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Recommended Citation
Dodge, Frederick Arthur, "A Study of Ionic Permeability Changes Underlying Excitation in Myelinated Nerve Fibers of the Frog" (1963). Student Theses and Dissertations. 602.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/602
Comments
A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy