BIOPHYSICAL THEORY AND MODELING |
A steady-state model of spreading depression predicts the
importance of an unknown conductance in specific dendritic
domains
Julia Makarova 1*, José M Ibarz 2, Santiago Canals 3 and Oscar Herreras 1
1 Instituto Cajal-C.S.I.C.
2 Hospital Ramón y Cajal
3 MPI for Biological Cybernetics
* To whom correspondence should be addressed. E-mail: makarovajulia{at}yahoo.es.
Submitted on June 23, 2006
Revised on August 23, 2006
Accepted on 8 February 2007
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Abstract |
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Spreading depression (SD) is a pathological wave of transient neuronal inactivation. We recently reported that the characteristic sustained complete depolarization is restricted to specific cell domains where the input resistance (Rin) first becomes negligible before achieving partial recovery, while in adjacent more polarized membranes it drops by much less. The experimental study of the participating membrane channels is hindered by their mixed contribution and heterogeneous distribution. Therefore, we derived a biophysical model to analyze the conductances that replicate the subcellular profile of Rin during SD. Systematic variation of conductance densities far beyond the ranges reported failed to fit the experimental values. Besides standard potassium, sodium, and Glu-mediated conductances, the initial opening and gradual closing of an as yet undetermined large conductance is required to account for the evolution of Rin. Potassium conductances follow in the relative contribution and their closing during the late phase is also predicted. Large intracellular potential gradients from zero to rest are readily sustained between shunted and adjacent SD-spared membranes, which remain electroregenerative. The gradients are achieved by a combination of high conductance subcellular domains and transmembrane ion redistribution in extended but discrete dendritic domains. We conclude that the heterogeneous subcellular behavior is due to local membrane properties, some of which may be specifically activated under extreme SD conditions.
Key Words:
depolarization gradients, input resistance, membrane shunt, neuron model, pyramidal cells, steady-state
