De Schutter: Purkinje Cell Model
|Figure 1: ||Activation and inactivation properties of the P-type calcium (CaP,
—) ionic conductances in the model. Seady-state activation and inactivation
vs. voltage are plotted at the left, the time constants of activation (τm) and
inactivation (τh) vs. voltage in the middle (Note: Semilogarithmic scale), and
a simulation of representative voltage-clamp currents at the right, obtained
from a spherical cell and assuming a complete block of all other channels.
They simulate steps from a holding potential of -110 to -70 mV up to 0 mV
in 10 mV increments. The voltage-clamp current amplitude has been scaled
arbitrarily because we mainly wanted to demonstrate the current kinetics.|
P-Type Calcium Current
The P-type Ca2+ channel is a high-threshold, very slowly inactivating channel
first described in the Purkinje cell . A complete whole-cell patch clamp study of
this channel in freshly dissociated rat Purkinje cells was done by ; this provided
us with all the data necessary to model the P-type calcium (CaP) current (Fig.
2C). Initial versions of the model were run with equations based on averaged
data  but, confirming our experience in other systems , we found that
equations based on data from a single preparation (Figs. 5C and 6C in ) made
Ca2+ spiking in the model more robust. These data do not support multiple
activation states for the CaP channel because there does not seem to be any
delay in activation  and the steady-state activation curve could be fitted
by a Boltzmann-style curve with power 1. Therefore activation of CaP
has been modeled with a single gate. This is in contrast to equations
for other mammalian Ca2+ currents, which usually show some delay in
activation [1, 6].
Recently, [9, 10] also reported CaP channel data on the basis of cell-attached
patch clamps of guinea pig Purkinje cells. These results seem to be in accord with
the data reported by  for activation; the threshold of activation especially is
very similar (-41 mV in 2 mM Ca2+ reported by Usowicz et al.  vs. -45 to -40 mV
in 5 mM Ba2+ . However, Usowicz et al.  show little or no inactivation of
CaP current, whereas  declares that there is a slow inactivation. Other authors
claim that there might be several time constants of inactivation for CaP
current  and to our knowledge a possible Ca2+-dependent inactivation, as
found in other high-threshold Ca2+ channels  has not been completely
excluded. The model used the slow inactivation suggested by  (Fig.
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