| | Models | Description |
| 1. |
Hysteresis in voltage gating of HCN channels (Elinder et al 2006, Mannikko et al 2005)
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We found that HCN2 and HCN4 channels
expressed in oocytes from the frog Xenopus laevis do not display the
activation kinetic changes that we (previously) observed in spHCN and
HCN1. However, HCN2 and HCN4 channels display changes in their tail
currents, suggesting that these channels also undergo mode shifts and
that the conformational changes underlying the mode shifts are due to
conserved aspects of HCN channels. With computer modelling, we show
that in channels with relatively slow opening kinetics and fast
mode-shift transitions, such as HCN2 and HCN4 channels, the mode shift
effects are not readily observable, except in the tail
kinetics. Computer simulations of sino-atrial node action potentials
suggest that the HCN2 channel, together with the HCN1 channel, are
important regulators of the heart firing frequency and that the mode
shift is an important property to prevent arrhythmic firing. We
conclude that although all HCN channels appear to undergo mode shifts
– and thus may serve to prevent arrhythmic firing
– it is mainly observable in ionic currents
from HCN channels with faster kinetics. See papers for more and details. |
| 2. |
Kesten and Langevin synaptic size fluctuation simulator (Hazan & Ziv 2020)
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Sizes of glutamatergic synapses vary tremendously, even when formed on the same neuron. This diversity is commonly thought to reflect the outcome of activity-dependent forms of synaptic plasticity, yet activity-independent processes might also play some part. In this paper we show that in neurons with no history of activity whatsoever, synaptic sizes are no less diverse. We show that this diversity is the product of activity-independent size fluctuations, which are sufficient to generate a full repertoire of synaptic sizes at correct proportions. This simulator shows how synaptic size fluctuations governed by a stochastic process known as a Kesten process (as well as a specific form of a non-linear Langevin process) can give rise to this size diversity. |
| 3. |
Stochastic LTP/LTD conditioning of a synapse (Migliore and Lansky 1999)
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Protracted presynaptic activity can induce long-term potentiation
(LTP) or long-term depression (LTD) of the synaptic strength. However,
virtually all the experiments testing how LTP and LTD depend on the
conditioning input are carried out with trains of stimuli at constant
frequencies, whereas neurons in vivo most likely experience a stochastic
variation of interstimulus intervals. We used a computational model of
synaptic transmission to test if and to what extent the stochastic
fluctuations of an input signal could alter the probability to change the
state of a synapse. See paper for conclusions. |
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