Computer simulations of the effect of non-inactivating sodium channels on the electric behavior of excitable cells.
Non-inactivating sodium channels have been discovered in various cell types. Additionally, normal voltage-gated sodium channels can be induced to lose their ability to inactivate by treatment with proteolytic enzymes, with certain chemical reagents, or with toxins. The presence of non-inactivating sodium channels in the outer membrane of a cell is expected to profoundly modify the electrical properties of the cell, because the electrical depolarization of the cell and the opening of these channels reciprocally reinforce each other without intrinsic control. The normal resting state may thus be destabilized and a new resting state at depolarized resting potentials may become possible. In this study, computer simulations were carried out to systematically explore the patterns of behavior of excitable cells which have non-inactivating sodium channels in their plasma membrane. The cells were assumed to be space clamped and the relevant Hodgkin and Huxley equations were assumed to describe the electrical behavior of the cells, except that some or all of the sodium channels could not inactivate. The sodium currents were thus represented by the sum of two terms: FI.gNa.m3.h.(V-ENa) + (1-FI).gNa.m3(V-ENa), where FI(0 less than or equal to FI less than or equal to 1) is the fraction of sodium channels which inactivate normally, and the other symbols have their usual significance. The behavior of non-inactivating sodium channels created by pronase treatment or reaction with chemical reagents was found to conform with that predicted by the second term in this expression. The simulations thus quantitatively apply to excitable cells thus treated, but may serve additionally to qualitatively illustrate patterns of electrical activity induced by non-inactivating sodium channels also in other cases. A variety of possible types of electrical behavior was obtained: Normal behavior, including capability of firing action potentials, requires values of FI which are not far from unity, the permissible range depending on the fully activated potassium ion conductance, gK. Bistability, at which the cell may exist in one of two stable states of different resting potential, occurs when the value of FI is lowered. Transitions from the polarized to the depolarized resting states, and vice versa, may be brought about by depolarizing and hyperpolarizing triggers, respectively. Such behavior is like that of memory storage devices. Monostability at depolarized potentials is favored by low FI values and can occur if gK is less than the Hodgkin and Huxley value.(ABSTRACT TRUNCATED AT 400 WORDS)
Steinberg
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IZ
Chemical Physics Department, Weizmann Institute of Science, Rehovot, Israel.
D000200:Action Potentials; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002468:Cell Physiological Phenomena; D003198:Computer Simulation; D004594:Electrophysiology; D008564:Membrane Potentials; D015222:Sodium Channels / Q000502:physiology*
D015222:Sodium Channels