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Transient potassium channels augment degeneracy in hippocampal active dendritic spectral tuning.

Rathour RK, Malik R, Narayanan R - Sci Rep (2016)

Bottom Line: Modeling studies have predicted a critical regulatory role for A-type potassium (KA) channels towards augmenting functional robustness of this map.Consistent with computational predictions, we found that blocking KA channels resulted in a significant reduction in resonance frequency and significant increases in input resistance, impedance amplitude and action-potential firing frequency across the somato-apical trunk.Our results unveil a pivotal role for fast transient channels in regulating theta-frequency spectral tuning and intrinsic phase response, and suggest that degeneracy with reference to several coexisting functional maps is mediated by cross-channel interactions across the active dendritic arbor.

View Article: PubMed Central - PubMed

Affiliation: Cellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.

ABSTRACT
Hippocampal pyramidal neurons express an intraneuronal map of spectral tuning mediated by hyperpolarization-activated cyclic-nucleotide-gated nonspecific-cation channels. Modeling studies have predicted a critical regulatory role for A-type potassium (KA) channels towards augmenting functional robustness of this map. To test this, we performed patch-clamp recordings from soma and dendrites of rat hippocampal pyramidal neurons, and measured spectral tuning before and after blocking KA channels using two structurally distinct pharmacological agents. Consistent with computational predictions, we found that blocking KA channels resulted in a significant reduction in resonance frequency and significant increases in input resistance, impedance amplitude and action-potential firing frequency across the somato-apical trunk. Furthermore, across all measured locations, blocking KA channels enhanced temporal summation of postsynaptic potentials and critically altered the impedance phase profile, resulting in a significant reduction in total inductive phase. Finally, pair-wise correlations between intraneuronal percentage changes (after blocking KA channels) in different measurements were mostly weak, suggesting differential regulation of different physiological properties by KA channels. Our results unveil a pivotal role for fast transient channels in regulating theta-frequency spectral tuning and intrinsic phase response, and suggest that degeneracy with reference to several coexisting functional maps is mediated by cross-channel interactions across the active dendritic arbor.

No MeSH data available.


Related in: MedlinePlus

Blocking KA channels had a larger effect on resonance frequency at depolarized potentials.(a) Percentage change in input resistance (represented as quartiles) measured at different membrane potentials and for various recording locations after blocking KA channels using BaCl2 (Kruskal-Wallis rank sum test, p = 0.47 for input resistance at soma; p = 0.19 for input resistance at ~125 μm; p = 0.29 for input resistance at ~250 μm). (b) Percentage change (mean ± SEM) in input resistance after blocking KA channels using BaCl2 plotted as a function of membrane potential. (c,d) Same as (a,b) but employing 3,4-DAP to block KA channels (Kruskal-Wallis rank sum test, p = 0.54 for input resistance at soma; p = 0.40 for input resistance at ~125 μm; p = 0.55 for input resistance at ~250 μm). (e) Percentage change in fR (represented as quartiles) measured at different membrane potentials and for various recording locations after blocking KA channels using BaCl2 (Kruskal-Wallis rank sum test, p < 0.05 for fR at soma; p < 0.001 for fR at ~125 μm; p < 0.01 for fR at ~250 μm; followed by Mann-Whitney U test, *p < 0.05). (f) Percentage change (mean ± SEM) in fR after blocking KA channels using BaCl2 plotted as a function of membrane potential. (g,h) Same as (e,f) but employing 3,4-DAP to block KA channels (Kruskal-Wallis rank sum test, p = 0.12 for fR at soma; p = 0.30 for fR at ~125 μm; p = 0.12 for fR at ~250 μm).
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f6: Blocking KA channels had a larger effect on resonance frequency at depolarized potentials.(a) Percentage change in input resistance (represented as quartiles) measured at different membrane potentials and for various recording locations after blocking KA channels using BaCl2 (Kruskal-Wallis rank sum test, p = 0.47 for input resistance at soma; p = 0.19 for input resistance at ~125 μm; p = 0.29 for input resistance at ~250 μm). (b) Percentage change (mean ± SEM) in input resistance after blocking KA channels using BaCl2 plotted as a function of membrane potential. (c,d) Same as (a,b) but employing 3,4-DAP to block KA channels (Kruskal-Wallis rank sum test, p = 0.54 for input resistance at soma; p = 0.40 for input resistance at ~125 μm; p = 0.55 for input resistance at ~250 μm). (e) Percentage change in fR (represented as quartiles) measured at different membrane potentials and for various recording locations after blocking KA channels using BaCl2 (Kruskal-Wallis rank sum test, p < 0.05 for fR at soma; p < 0.001 for fR at ~125 μm; p < 0.01 for fR at ~250 μm; followed by Mann-Whitney U test, *p < 0.05). (f) Percentage change (mean ± SEM) in fR after blocking KA channels using BaCl2 plotted as a function of membrane potential. (g,h) Same as (e,f) but employing 3,4-DAP to block KA channels (Kruskal-Wallis rank sum test, p = 0.12 for fR at soma; p = 0.30 for fR at ~125 μm; p = 0.12 for fR at ~250 μm).

Mentions: As resonating properties depend heavily on membrane potential, and different channels alter excitability and resonance properties differentially at different membrane voltages depending on their activation-inactivation voltage ranges712141825, we employed voltage-dependence of physiological measurements as an additional tool to assess the specificity of the measurements to KA channel blockade. Specifically, hippocampal KA channels are active at depolarized voltages beyond −70 mV, with the window component of the KA current active in the voltage range between −70 mV to −20 mV2021. Therefore, the impact of blocking KA channels on physiological measurements should be higher at more depolarized potentials than at hyperpolarized potentials (in the subthreshold range). Additionally, as steady-state measurements (like Rin) are critically dependent on the window component of the KA current720, and an effect of KA channels on physiological measurements should be consistent with the channel activation range, we probed the impact of blocking KA channels on the voltage-dependence (range: −75 to −60 mV) of these measurements (Fig. 6, S1). We found that the impact of blocking KA channels on fR was graded as a function of membrane voltage, with a significantly higher impact at depolarized voltages compared to their hyperpolarized counterparts (Fig. 6e–h, see Supplementary Fig. S1). Similar trends were observed in Rin, /Z/max and other measurements as well (Fig. 6a–d, see Supplementary Fig. S1), thereby providing an additional line of evidence that the observed changes were specific to blockade of KA channels. Specifically, as expected from the increased excitability that resulted from blocking KA channels (Fig. 2) and as predicted by computational models2, we found that the maximum impedance amplitude /Z/max increased after KA-channel blockade (Fig. 4c, see Supplementary Figs S1f and S1l), with percentage differences not very different across locations (see Supplementary Fig. S1f).


Transient potassium channels augment degeneracy in hippocampal active dendritic spectral tuning.

Rathour RK, Malik R, Narayanan R - Sci Rep (2016)

Blocking KA channels had a larger effect on resonance frequency at depolarized potentials.(a) Percentage change in input resistance (represented as quartiles) measured at different membrane potentials and for various recording locations after blocking KA channels using BaCl2 (Kruskal-Wallis rank sum test, p = 0.47 for input resistance at soma; p = 0.19 for input resistance at ~125 μm; p = 0.29 for input resistance at ~250 μm). (b) Percentage change (mean ± SEM) in input resistance after blocking KA channels using BaCl2 plotted as a function of membrane potential. (c,d) Same as (a,b) but employing 3,4-DAP to block KA channels (Kruskal-Wallis rank sum test, p = 0.54 for input resistance at soma; p = 0.40 for input resistance at ~125 μm; p = 0.55 for input resistance at ~250 μm). (e) Percentage change in fR (represented as quartiles) measured at different membrane potentials and for various recording locations after blocking KA channels using BaCl2 (Kruskal-Wallis rank sum test, p < 0.05 for fR at soma; p < 0.001 for fR at ~125 μm; p < 0.01 for fR at ~250 μm; followed by Mann-Whitney U test, *p < 0.05). (f) Percentage change (mean ± SEM) in fR after blocking KA channels using BaCl2 plotted as a function of membrane potential. (g,h) Same as (e,f) but employing 3,4-DAP to block KA channels (Kruskal-Wallis rank sum test, p = 0.12 for fR at soma; p = 0.30 for fR at ~125 μm; p = 0.12 for fR at ~250 μm).
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f6: Blocking KA channels had a larger effect on resonance frequency at depolarized potentials.(a) Percentage change in input resistance (represented as quartiles) measured at different membrane potentials and for various recording locations after blocking KA channels using BaCl2 (Kruskal-Wallis rank sum test, p = 0.47 for input resistance at soma; p = 0.19 for input resistance at ~125 μm; p = 0.29 for input resistance at ~250 μm). (b) Percentage change (mean ± SEM) in input resistance after blocking KA channels using BaCl2 plotted as a function of membrane potential. (c,d) Same as (a,b) but employing 3,4-DAP to block KA channels (Kruskal-Wallis rank sum test, p = 0.54 for input resistance at soma; p = 0.40 for input resistance at ~125 μm; p = 0.55 for input resistance at ~250 μm). (e) Percentage change in fR (represented as quartiles) measured at different membrane potentials and for various recording locations after blocking KA channels using BaCl2 (Kruskal-Wallis rank sum test, p < 0.05 for fR at soma; p < 0.001 for fR at ~125 μm; p < 0.01 for fR at ~250 μm; followed by Mann-Whitney U test, *p < 0.05). (f) Percentage change (mean ± SEM) in fR after blocking KA channels using BaCl2 plotted as a function of membrane potential. (g,h) Same as (e,f) but employing 3,4-DAP to block KA channels (Kruskal-Wallis rank sum test, p = 0.12 for fR at soma; p = 0.30 for fR at ~125 μm; p = 0.12 for fR at ~250 μm).
Mentions: As resonating properties depend heavily on membrane potential, and different channels alter excitability and resonance properties differentially at different membrane voltages depending on their activation-inactivation voltage ranges712141825, we employed voltage-dependence of physiological measurements as an additional tool to assess the specificity of the measurements to KA channel blockade. Specifically, hippocampal KA channels are active at depolarized voltages beyond −70 mV, with the window component of the KA current active in the voltage range between −70 mV to −20 mV2021. Therefore, the impact of blocking KA channels on physiological measurements should be higher at more depolarized potentials than at hyperpolarized potentials (in the subthreshold range). Additionally, as steady-state measurements (like Rin) are critically dependent on the window component of the KA current720, and an effect of KA channels on physiological measurements should be consistent with the channel activation range, we probed the impact of blocking KA channels on the voltage-dependence (range: −75 to −60 mV) of these measurements (Fig. 6, S1). We found that the impact of blocking KA channels on fR was graded as a function of membrane voltage, with a significantly higher impact at depolarized voltages compared to their hyperpolarized counterparts (Fig. 6e–h, see Supplementary Fig. S1). Similar trends were observed in Rin, /Z/max and other measurements as well (Fig. 6a–d, see Supplementary Fig. S1), thereby providing an additional line of evidence that the observed changes were specific to blockade of KA channels. Specifically, as expected from the increased excitability that resulted from blocking KA channels (Fig. 2) and as predicted by computational models2, we found that the maximum impedance amplitude /Z/max increased after KA-channel blockade (Fig. 4c, see Supplementary Figs S1f and S1l), with percentage differences not very different across locations (see Supplementary Fig. S1f).

Bottom Line: Modeling studies have predicted a critical regulatory role for A-type potassium (KA) channels towards augmenting functional robustness of this map.Consistent with computational predictions, we found that blocking KA channels resulted in a significant reduction in resonance frequency and significant increases in input resistance, impedance amplitude and action-potential firing frequency across the somato-apical trunk.Our results unveil a pivotal role for fast transient channels in regulating theta-frequency spectral tuning and intrinsic phase response, and suggest that degeneracy with reference to several coexisting functional maps is mediated by cross-channel interactions across the active dendritic arbor.

View Article: PubMed Central - PubMed

Affiliation: Cellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.

ABSTRACT
Hippocampal pyramidal neurons express an intraneuronal map of spectral tuning mediated by hyperpolarization-activated cyclic-nucleotide-gated nonspecific-cation channels. Modeling studies have predicted a critical regulatory role for A-type potassium (KA) channels towards augmenting functional robustness of this map. To test this, we performed patch-clamp recordings from soma and dendrites of rat hippocampal pyramidal neurons, and measured spectral tuning before and after blocking KA channels using two structurally distinct pharmacological agents. Consistent with computational predictions, we found that blocking KA channels resulted in a significant reduction in resonance frequency and significant increases in input resistance, impedance amplitude and action-potential firing frequency across the somato-apical trunk. Furthermore, across all measured locations, blocking KA channels enhanced temporal summation of postsynaptic potentials and critically altered the impedance phase profile, resulting in a significant reduction in total inductive phase. Finally, pair-wise correlations between intraneuronal percentage changes (after blocking KA channels) in different measurements were mostly weak, suggesting differential regulation of different physiological properties by KA channels. Our results unveil a pivotal role for fast transient channels in regulating theta-frequency spectral tuning and intrinsic phase response, and suggest that degeneracy with reference to several coexisting functional maps is mediated by cross-channel interactions across the active dendritic arbor.

No MeSH data available.


Related in: MedlinePlus