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William F Podlaski

Alexander Seeholzer

Lukas N Groschner

Gero Miesenböck

Rajnish Ranjan

Tim P Vogels

(2017)
Mapping the function of neuronal ion channels in model and experiment

eLife 6:e22152.

https://doi.org/10.7554/eLife.22152
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Figures
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Additional files

7 figures, 2 tables and 2 additional files

Figures

Figure 1

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The choice of ion channel model influences the behavior of a simulated neuron.

(A) Biophysical neuron models are composed of a detailed multicompartmental morphology, several active ion channel conductances, and a density of each conductance that depends on the specific …
https://doi.org/10.7554/eLife.22152.002

Figure 2

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Ion channel models can be categorized by metadata and ancestor-descendant relationships.

(A) Metadata were manually extracted from ModelDB and associated journal articles (top). Ancestor-descendant relationship (bottom) was established between different models (see main text for …
https://doi.org/10.7554/eLife.22152.003

Figure 2—source data 1 Table of subtypes for each ion type class. Subtypes of each of the five classes currently available in the resource (Kv, Nav, Cav, KCa, Ih), sorted by the frequency of their occurrence.: https://doi.org/10.7554/eLife.22152.004
Download elife-22152-fig2-data1-v1.xlsx

Figure 3 with 4 supplements

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Voltage-clamp protocols for the quantitative analysis of ion channel models.

(A) Left: five voltage clamp protocols were used to characterize ion channel responses recorded in single compartment somata simulated in *NEURON* (see Figure 3—figure supplement 1 and Tables 1 and 2 …
https://doi.org/10.7554/eLife.22152.005

Figure 3—source data 1 Table of omitted files. List of omitted files for each of the five ion type classes, with a brief description of the reason for omission.: https://doi.org/10.7554/eLife.22152.006
Download elife-22152-fig3-data1-v1.xlsx

Figure 3—figure supplement 1

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Graphical description of the five voltage-clamp protocols used for ion channel model analysis.

Activation (A), inactivation (B), deactivation (C), ramp (D), action potential (E). See Table 2 for values of variables used in simulations. Dashed lines represent the approximate regions used for …
https://doi.org/10.7554/eLife.22152.007

Figure 3—figure supplement 2

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Cluster indexes for Kv and Nav classes.

See Materials and methods for description. ‘Singletons’ refers to the number of single-element clusters. (A) Cluster indexes of the Kv class. The cluster number 60 was chosen since Dunn and …
https://doi.org/10.7554/eLife.22152.008

Figure 3—figure supplement 3

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Cluster indexes for Cav, KCa and Ih classes.

Cluster indexes, see Materials and methods for description. ‘Singletons’ refers to the number of single-element clusters. (A) Cluster indexes of the Cav class. The candidate cluster number 30 (peak …
https://doi.org/10.7554/eLife.22152.009

Figure 3—figure supplement 4

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Comparison of intra- and inter-subtype variability with intra- and inter-cluster variability.

(A) Median pairwise distance between all channels of a given subtype, calculated either with the final score (‘total’), or only each of the intermediate condition scores (here abbreviated, cf. Figure…
https://doi.org/10.7554/eLife.22152.010

Figure 4 with 2 supplements

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Quantitative analysis of Kv ion channel models: functional map and clusters of common behavior.

(A) Pedigree graph of the Kv class (cf. Figure 2E), colored by membership in the 11 largest clusters in the class (named by most prevalent subtype, bottom). Membership to other clusters is indicated …
https://doi.org/10.7554/eLife.22152.011

Figure 4—figure supplement 1

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Nav and Cav class genealogy and clustering.

(A) Families of the Nav class, ordered from left to right by family size. Each dot represents an ion channel model and edges represent family relationships. Colors indicate the 11 most prevalent …
https://doi.org/10.7554/eLife.22152.012

Figure 4—figure supplement 2

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KCa and Ih class genealogy and clustering.

(A) Families of the KCa class, ordered from left to right by family size. Each dot represents an ion channel model and edges represent family relationships. Colors indicate the 11 subtypes in the …
https://doi.org/10.7554/eLife.22152.013

Figure 5

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Ion channel model groups defined by common subtype, neuron type and brain area show variability in behavior.

(A) Kv models are grouped by common subtype, neuron type, and brain area. The mean pairwise distance in score space between all models within a group is plotted against group size, with errorbars …
https://doi.org/10.7554/eLife.22152.014

Figure 6 with 1 supplement

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Automated analysis of new models and experimental data.

(A) Flowchart of data processing steps involved in automated comparison. Source code for model files written in *NEURON* can be uploaded to the website, and current responses are automatically …
https://doi.org/10.7554/eLife.22152.015

Figure 6—figure supplement 1

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K+ current recordings from Drosophila Kenyon cells.

Recordings from eight example traces of K+ current from Drosophila Kenyon cells (gray), with average (black). See Materials and methods for a description of experiments. Response traces are arranged …
https://doi.org/10.7554/eLife.22152.016

Figure 7

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The ICGenealogy website allows for the interactive visualization of all data and analysis on the resource (ICGenealogy, 2016) (http://icg.neurotheory.ox.ac.uk).

(A) Schematic of similarity view on website. Channel models of the Kv family are displayed in the first two principal components of score space, colored by subtype (legend on left). Hovering over …
https://doi.org/10.7554/eLife.22152.017

Tables

Table 1

Parameters for reversal potential and inside and outside concentrations used in simulation protocols for five ion type classes. Ionic concentrations were not used for Ih currents.

https://doi.org/10.7554/eLife.22152.018

	$E_{r e v}$ (mV)	${[i o n]}_{i n}$ (mM)	${[i o n]}_{o u t}$ (mM)
Kv	−86.7	85.0	3.3152396
Nav	50.0	21.0	136.3753955
Cav	135.0	8.1929e-5	2.0
KCa	−86.7	85.0	3.3152396
Ih	−45.0	−	−

Table 2

Voltage-clamp protocol parameters for the five ion type classes. Times are stated in units of ms, voltages in units of mV. See Figure 3—figure supplement 1 for graphical description. Items $T_{A}^{*}$ and $T_{B}^{*}$ …

https://doi.org/10.7554/eLife.22152.019

Act	Ion type	$V_{0}$	$V_{1}$	$V_{2}$	$Δ V$	$T_{1}$	$T_{2}$	$T_{3}$	$T_{A}^{*}$	$T_{B}^{*}$
	Kv	−80	−80	70	10	100	500	100	100	700
	Nav	−80	−80	70	10	20	50	30	18	100
	Cav	−80	−80	70	10	100	500	100	98	700
	KCa	−80	−80	70	10	100	500	100	95	605
	Ih	−40	−150	0	10	100	2000	100	95	2105
Inact	Ion Type	$V_{0}$	$V_{1}$	$V_{2}$	$V_{3}$	$Δ V$	$T_{1}$	$T_{2}$	$T_{3}$	$T_{4}$	$T_{A}^{*}$	$T_{B}^{*}$
	Kv	−80	−40	70	30	10	100	1500	50	100	1600	1700
	Nav	−80	−40	70	30	10	100	1500	50	100	1580	1750
	Cav	−80	−40	70	30	10	100	1500	50	100	1580	1750
	KCa	−80	−40	70	30	10	100	1500	50	100	1595	1700
	Ih	−40	−150	−40	−120	10	100	1000	300	100	1095	1405
Deact	Ion Type	$V_{0}$	$V_{1}$	$V_{2}$	$V_{3}$	$Δ V$	$T_{1}$	$T_{2}$	$T_{3}$	$T_{4}$	$T_{A}^{*}$	$T_{B}^{*}$
	Kv	−80	70	−100	40	10	100	300	200	100	400	600
	Nav	−80	70	−100	40	10	20	10	30	20	29	80
	Cav	−80	70	−100	40	10	100	300	200	100	380	700
	KCa	−80	70	−100	40	10	100	300	200	100	395	605
	Ih	−40	−140	−110	0	10	100	1500	500	400	1595	2105
Ramp	Ion Type	$V_{0}$	$V_{1}$	$T_{1}$	$T_{2}$	$T_{3}$	$T_{4}$	$T_{5}$	$T_{6}$	$T_{7}$	$T_{8}$	$T_{9}$	$T_{A}^{*}$	$T_{B}^{*}$
	Kv	−80	70	100	800	400	400	400	200	400	100	100	100	2800
	Nav	−80	70	100	800	400	400	400	200	400	100	100	98	2800
	Cav	−80	70	100	800	400	400	400	200	400	100	100	98	2800
	KCa	−80	70	100	800	400	400	400	200	400	100	100	100	2800
	Ih	−80	70	100	800	400	400	400	200	400	100	100	100	2800
AP	Ion Type	$T_{1}$	$T_{A}^{*}$	$T_{B}^{*}$
	Kv	1800	100	1800
	Nav	1800	98	1800
	Cav	1800	98	1800
	KCa	1800	95	1655
	Ih	1800	95	1655

Additional files

Supplementary file 1 Instruction manual for ICGenealogy website browser. This file contains a brief tutorial which introduces all of the major aspects of the accompanying web browser for the database.: https://doi.org/10.7554/eLife.22152.020
Download elife-22152-supp1-v1.pdf
Supplementary file 2 Supplementary references. This file lists all model files contained in the database and used for analysis here, as well as the accompanying reference publication for each one.: https://doi.org/10.7554/eLife.22152.021
Download elife-22152-supp2-v1.pdf

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Figures

The choice of ion channel model influences the behavior of a simulated neuron.

Ion channel models can be categorized by metadata and ancestor-descendant relationships.

Figure 2—source data 1

Voltage-clamp protocols for the quantitative analysis of ion channel models.

Figure 3—source data 1

Graphical description of the five voltage-clamp protocols used for ion channel model analysis.

Cluster indexes for Kv and Nav classes.

Cluster indexes for Cav, KCa and Ih classes.

Comparison of intra- and inter-subtype variability with intra- and inter-cluster variability.

Quantitative analysis of Kv ion channel models: functional map and clusters of common behavior.

Nav and Cav class genealogy and clustering.

KCa and Ih class genealogy and clustering.

Ion channel model groups defined by common subtype, neuron type and brain area show variability in behavior.

Automated analysis of new models and experimental data.

K+ current recordings from Drosophila Kenyon cells.

The ICGenealogy website allows for the interactive visualization of all data and analysis on the resource (ICGenealogy, 2016) (http://icg.neurotheory.ox.ac.uk).

Tables

Additional files

Supplementary file 1

Supplementary file 2

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The choice of ion channel model influences the behavior of a simulated neuron.

Ion channel models can be categorized by metadata and ancestor-descendant relationships.

Figure 2—source data 1

Voltage-clamp protocols for the quantitative analysis of ion channel models.

Figure 3—source data 1

Graphical description of the five voltage-clamp protocols used for ion channel model analysis.

Cluster indexes for Kv and Nav classes.

Cluster indexes for Cav, KCa and Ih classes.

Comparison of intra- and inter-subtype variability with intra- and inter-cluster variability.

Quantitative analysis of Kv ion channel models: functional map and clusters of common behavior.

Nav and Cav class genealogy and clustering.

KCa and Ih class genealogy and clustering.

Ion channel model groups defined by common subtype, neuron type and brain area show variability in behavior.

Automated analysis of new models and experimental data.

K+ current recordings from Drosophila Kenyon cells.

The ICGenealogy website allows for the interactive visualization of all data and analysis on the resource (ICGenealogy, 2016) (http://icg.neurotheory.ox.ac.uk).

Supplementary file 1

Supplementary file 2