A model of inward and outward membrane currents in cultured embryonic amphibian spinal neurons and reconstruction of the action potential.
A model of the membrane currents in embryonic amphibian neurons has been developed in order to investigate the ionic mechanisms underlying developmental changes in excitability. Differentiating amphibian neurons both in situ and in vitro show a gradual change in the ionic sensitivity of their action potential from Ca- to Na-dependent, with an intermediate period in which the action potential shows a mixed ionic sensitivity. The model developed incorporates quantitative descriptions of Na, Ca and voltage-dependent K currents recorded (using whole-cell gigaohm-seal recording techniques) from presumptive neurons isolated from neural plate stage embryos of the axolotl Amblystoma during their in vitro differentiation. The kinetic descriptions of the currents were developed using the form of those of Hodgkin and Huxley. Na and K currents were modeled as voltage-dependent conductances showing m3h and n4 kinetics, respectively. Ca current was modeled (using the constant field relation) as a voltage-dependent permeability with s2 activation kinetics. Ca currents in whole-cell recordings were non-inactivating, and no inactivation mechanism was specified in the model. When modeled current amplitudes and kinetics were scaled as appropriate for a cell at an intermediate stage of differentiation (when the action potential recorded with microelectrodes shows a mixed Na- and Ca-dependence), the action potential predicted by the model showed a similar waveform and ionic dependence. The utility of this model lies in its ability to indicate the activity of each ionic current during an action potential at any developmental stage, and to unambiguously test the effects on neuronal excitability of alterations in the magnitude and/or kinetics of any of the ionic currents present in the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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D000200:Action Potentials; D000557:Ambystoma; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian; D007473:Ion Channels / Q000502:physiology*; D009473:Neuronal Plasticity; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013116:Spinal Cord / Q000502:physiology*
D007473:Ion Channels; D012964:Sodium; D011188:Potassium; D002118:Calcium