Simulator Parameter Considerations
The value of the predictions made by the simulator depends on the accuracy of the parameters
used for calculation. This page is intended to give guidance with regard to what parameters are most important and what numeric values to use.
Cochlear Dimensions
The size of the cochlea is one of the most important factors. The simulator has cochlear dimensions
(i.e. the cross-sectional area of each scala as a function of distance) programmed in for 6 species, including
human, guinea pig, rat, mouse, gerbil and bat.
These dimensions have been derived from images obtained by 3-D magnetic resonance microscopy,
as summarized in the page titled "Dimensions of Inner Ear Fluid Spaces".
Be aware that for the human cochlea there are no area versus distance data available for the endolymphatic
space and for this space the profile is presently estimated.
Diffusion Coefficients
The speed that each solute spreads depends on how large it is, so it is essential to set a diffusion coefficient
approriate to the solute you are using. A listing of diffusion coefficients and
their dependence on molecular size are
detailed here. Diffusion coefficients for some substances are incorporated into the model,
or an estimate can be used based on the formula weight of the substance in question.
Longitudinal Flow of Fluids
An important factor which affects spread of solutes is the presence or absence of longitudinal volume flow in the scalae.
This can be set in the model by selecting the <Perfusion/Flow > option on the < Injections > page. For many conditions
longitudinal flow can be ignored as flow rates in the sealed cochlea are extremely low (basally-directed 0.0008 mm/min in endolymph;
apically-directed 0.0016 ul/min in ST perilymph). Measured flow rates are summarized on
the "Longitudinal Flow Rate of Cochlear Fluids" page. The exception to this situation is when you
are simulating an experiment with the perilymphatic space perforated, such as perfusion. Under these conditions, CSF enters the
cochlea through the cochlear aqueduct and causes longitudinal flow from the base of scala tympani to the site of the outlet. In the model,
such a flow can be set either from the <Perfusion/Flow > option on the < Injections > page, or by checking the
<Perilymphatic Leak Present > option on the <Communications> page. In either case you must enter the rate of flow, which is typically
0.5 - 1.0 ul/min in the perforated guinea pig cochlea. In the model, flows of endolymph and perilymph are independent and flow between
endolymphatic and perilymphatic spaces is not available. Flow values are applicable to all solutes
Permeability of the Round Window Membrane
Although a number of studies have documented passage of solutes through the round window membrane, none has yet quantified entry in terms
of round window permeability.
Using the simulator it may be possible it estimate permeability values from these data, although this has
not yet been performed.
Round window permeability can only be approximated until more quantitative data become available.
Round window permeability values are solute-specific.
Communications between Endolymph and Perilymph
Solute movements are calculated as clearance, from one scala to another.
In the simulator, clearance is defined by setting the half-time of the process in scala media.
As endolymphatic and perilymphatic scalae have different cross-sectional areas, movement of
solute does not result in the same rate constant / half time in both scalae.
Although we have limited data for clearances, these values are solute-specific
and we really need data for more substances. It is notable that, in general, anions are cleared more slowly from endolymph
than cations due to the effects of the endocochlear potential.
Communications between Scala Tympani and Scala Vestibuli
Via the helicotrema
Both solute diffusion and perilymph flow between scala tumpani and scala vestibuli across the helicotrema (at the apex) is incorporated in to the simulator.
It can be disabled by a toggle switch on the <Communications> page.
Radially across the spiral ligament
The movements of solutes between scala tympani and scala vestibuli via radial pathways
(locally in each turn rather than via the helicotrema)
have been well-documented. This has been quantified for the marker, TMPA, but not yet for other solutes.
We need more data in this area.
Clearance to blood/ Entry from blood
Again, we have limited data for some solutes, but much of this is made more complex by the many potential
clearance mechanisms which may be invoked. In some cases it is acceptable to combine all processes into
one parameter appropriate to a specific experimental condition.