An active membrane model of the cerebellar Purkinje cell I. Simulation of current clamps in slice

E. De Schutter, J. M. Bower

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292 Scopus citations


1. A detailed compartmental model of a cerebellar Purkinje cell with active dendritic membrane was constructed. The model was based on anatomic reconstructions of single Purkinje cells and included 10 different types of voltage-dependent channels described by Hodgkin-Huxley equations, derived from Purkinje cell-specific voltage-clamp data where available. These channels included a fast and persistent Na+ channel, three voltage-dependent K+ channels. T-type and P-type Ca2+ channels, and two types of Ca2+- activated K+ channels. 2. The ionic channels were distributed differentially over three zones of the model, with Na+ channels in the soma, fast K+ channels in the soma and main dendrite, and Ca2+ channels and Ca2+- activated K+ channels in the entire dendrite. Channel densities in the model were varied until it could reproduce Purkinje cell responses to current injections in the soma or dendrite, as observed in slice recordings. 3. As in real Purkinje cells, the model generated two types of spiking behavior. In response to small current injections the model fired exclusively fast somatic spikes. These somatic spikes were caused by Na+ channels and repolarized by the delayed rectifier. When higher-amplitude current injections were given, sodium spiking increased in frequency until the model generated large dendritic Ca2+ spikes. Analysis of membrane currents underlying this behavior showed that these Ca2+ spikes were caused by the P-type Ca2+ channel and repolarized by the BK-type Ca2+-activated K+ channel. As in pharmacological blocking experiments, removal of Na+ channels abolished the fast spikes and removal of Ca2+ channels removed Ca2+ spiking. 4. In addition to spiking behavior, the model also produced slow plateau potentials in both the dendrite and soma. These longer-duration potentials occurred in response to both short and prolonged current steps. Analysis of the model demonstrated that the plateau potentials in the soma were caused by the window current component of the fast Na+ current, which was much larger than the current through the persistent Na+ channels. Plateau potentials in the dendrite were carried by the same P-type Ca2+ channel that was also responsible for Ca2+ spike generation. The P channel could participate in both model functions because of the low-threshold K2-type Ca2+-activated K+ channel, which dynamically changed the threshold for dendritic spike generation through a negative feedback loop with the activation kinetics of the P-type Ca2+ channel. 5. These model responses were robust to changes in the densities of all of the ionic channels. For most of the channels, modifying their densities by factors of ≥2 resulted only in left or right shifts of the frequency-current curve. However, changes of >20% to the amount of P-type Ca2+ channels or of one of the Ca2+-activated K+ channels in the model either suppressed dendritic spikes or caused the model to always fire Ca2+ spikes. Modeling results were also robust to variations in Purkinje cell morphology. We simulated models of two other anatomically reconstructed Purkinje cells with the same channel distributions and got similar responses to current injections. 6. The model was used to compare the electrotonic length of the Purkinje cell in the presence and absence of active dendritic conductances. The electrotonic distance from soma to the tip of the most distal dendrite increased from 0.57 λ in a passive model to 0.95 λ in a quiet model with active membrane. During a dendritic spike generated by current injection the distance increased even more, to 1.57 λ. 7. Finally, the model was used to study the probable accuracy of experimental voltage-clamp data. Whole-cell patch-clamp conditions were simulated by blocking most of the K+ currents in the model. The increased electrotonic length due to the active dendritic membrane caused space clamp to fail, resulting in membrane potentials in proximal and distal dendrites that differed critically from the holding potential in the soma.

Original languageEnglish (US)
Pages (from-to)375-400
Number of pages26
JournalJournal of neurophysiology
Issue number1
StatePublished - 1994

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology


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