Modeling the excitability of the cerebellar Purkinje cell with detailed calcium dynamics
© Anwar et al; licensee BioMed Central Ltd. 2009
Published: 13 July 2009
Previous studies have suggested that the activity pattern of a cerebellar Purkinje cells (PC) is significantly controlled by voltage activated Ca2+ channels and Ca2+ activated K+ channels, present mainly on its elaborate dendritic tree . Although the main somatic excitatory drive propagates very weakly into the dendritic tree , somehow a significant interaction between somatic and dendritic spiking occurs. Ca2+ entering through P-type channel is thought to be the main source of this excitability modulation, and this Ca2+ influx also activates large conductance (BK) and small conductance (SK) Ca2+ dependent K+ channels [1, 3]. This interaction often results in the counter-intuitive computational somatic and dendritic spiking behavior of PCs , but nevertheless this important aspect has not been thoroughly investigated in previous computational modeling studies.
In this work, we try to integrate known aspects of Ca2+ dynamics in PC dendrites by building a new model, which would help us understand the consequent computational properties of a PC. Recently, it has been shown that BK channels are in close vicinity of Ca2+ sources as compared to SK channels , suggesting that BK channels require a brief large amount (~10–100 μM) of Ca2+ whereas SK channels require a long yet small quantity (~0.1–2 μM) of Ca2+ for the activation. Therefore it might be interesting to see how this spatiotemporal interaction of Ca2+ sources with Ca2+ activated K+ channels takes place in simulation. Due to lack of sufficient experimental data about the interaction between Ca2+ sources and Ca2+ activated channels in PCs, we could only capture temporal interaction by including Ca2+ dynamics with several buffers and pumps  in our model. We expect that this will be sufficient to activate the BK and SK channel correctly. In addition to introducing complex Ca2+ dynamics to our model, we also built new kinetic models of the P-type Ca2+ channel and BK channel based on the recent experimental data  and gating kinetics with both voltage and Ca2+ dependence .
Not only the composition of active ionic mechanisms, the dendritic morphology can also significantly modify the spiking pattern . However, simulation on the detailed reconstructed morphology of a PC dendritic tree is not suitably efficient for parameter tuning to obtain a desired behavior. Therefore, to investigate the morphological significance in firing behaviors, we have built and used an electrotonically accurate reduced morphology of a PC as well as an even simpler three-compartment model comprising of soma, smooth dendrite and spiny dendrite.
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