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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

Bath application of 50 μM BaCl2 introduced small but significant differences in certain subthreshold measurements at hyperpolarized, but not depolarized, voltages.(a) Schematic showing experimental setup for assessing the effect of bath application of 50 μM BaCl2 on various physiologically relevant measurements at the soma. The experimental protocol was the same as that depicted in Fig. 1a, with the only difference being the reduction in the concentration of BaCl2 from 200 μM to 50 μM. (b) Voltage response of an example cell to constant current injection for 700 ms of varying amplitude, from −50 to +50 pA in steps of 10 pA, under baseline condition (blue) and after application of 50 μM BaCl2 (orange). (c) Top, voltage traces in response to a train of five α-EPSCs at 20 Hz under baseline condition (blue) and after application of 50 μM BaCl2 (orange). Voltage traces, in response to a pulse current of 200 pA for 700 ms, recorded from the soma under baseline condition (blue) and after application of 50 μM BaCl2 (orange). (d) Voltage traces recorded from the soma in response to the Chirp15 stimulus under baseline condition (blue) and after application of 50 μM BaCl2 (orange). All traces in (b–d) were recorded from the same neuron. (e,f) Impedance amplitude (e) and phase (f) plotted as functions of input current frequency derived from corresponding color-matched traces shown in (d). (g–o) Population data (n = 8; mean ± SEM) for the effect of applying 50 μM BaCl2 on input resistance (g); input resistance (h) and sag ratio (i) as functions of voltage; temporal summation strength (j); action potential firing frequency for different current injections (k); and resonance frequency (l), total inductive phase (m), resonance strength (n) and maximal impedance amplitude (o) as functions of voltage. For (g–o), *p < 0.05 for paired Student’s t test, baseline measurements are depicted in blue and measurements obtained after application of 50 μM BaCl2 are plotted in orange.
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f7: Bath application of 50 μM BaCl2 introduced small but significant differences in certain subthreshold measurements at hyperpolarized, but not depolarized, voltages.(a) Schematic showing experimental setup for assessing the effect of bath application of 50 μM BaCl2 on various physiologically relevant measurements at the soma. The experimental protocol was the same as that depicted in Fig. 1a, with the only difference being the reduction in the concentration of BaCl2 from 200 μM to 50 μM. (b) Voltage response of an example cell to constant current injection for 700 ms of varying amplitude, from −50 to +50 pA in steps of 10 pA, under baseline condition (blue) and after application of 50 μM BaCl2 (orange). (c) Top, voltage traces in response to a train of five α-EPSCs at 20 Hz under baseline condition (blue) and after application of 50 μM BaCl2 (orange). Voltage traces, in response to a pulse current of 200 pA for 700 ms, recorded from the soma under baseline condition (blue) and after application of 50 μM BaCl2 (orange). (d) Voltage traces recorded from the soma in response to the Chirp15 stimulus under baseline condition (blue) and after application of 50 μM BaCl2 (orange). All traces in (b–d) were recorded from the same neuron. (e,f) Impedance amplitude (e) and phase (f) plotted as functions of input current frequency derived from corresponding color-matched traces shown in (d). (g–o) Population data (n = 8; mean ± SEM) for the effect of applying 50 μM BaCl2 on input resistance (g); input resistance (h) and sag ratio (i) as functions of voltage; temporal summation strength (j); action potential firing frequency for different current injections (k); and resonance frequency (l), total inductive phase (m), resonance strength (n) and maximal impedance amplitude (o) as functions of voltage. For (g–o), *p < 0.05 for paired Student’s t test, baseline measurements are depicted in blue and measurements obtained after application of 50 μM BaCl2 are plotted in orange.

Mentions: BaCl2 is an established blocker of certain types of inward-rectifying potassium (KIR) channels2627 at lower concentrations (50 μM). This implies that KIR channels were also blocked in our experiments with BaCl2, where we had employed BaCl2 at 200 μM to block KA channels22. What was the contribution of KIR channels to the changes (Figs 2, 3, 4, 5, 6, Fig. S1) in intrinsic excitability, spectral selectivity and phase tuning observed with BaCl2 as the pharmacological agent? Could the voltage-dependence of intrinsic measurements be explained with blockade of KIR channels? To answer these questions directly, we measured changes in intrinsic properties before and after application of 50 μM BaCl2, a concentration where BaCl2-induced blockade of KIR channels is more efficacious than that of KA channels. We found that 50 μM BaCl2 was insufficient to elicit significant differences in Rin, firing frequency or temporal summation (Fig. 7b,c,g,j,k). Additionally, when we assessed intrinsic measurements as functions of membrane voltage, in striking contrast to our results with 200 μM BaCl2 (Fig. 6, Fig. S1), we found that 50 μM BaCl2 was insufficient to introduce significant changes in any of the measurements at depolarized potentials (Fig. 7h,i,k–o). Significant effects of applying 50 μM BaCl2 were confined to measurements at hyperpolarized voltages, specifically in (Fig. 7h), fR (Fig. 7l) and /Z/max (Fig. 7o), thereby ruling out a role for KIR channels in introducing significant changes observed in depolarizing potentials (with 200 μM BaCl2). Together, these results argue against a significant role for KIR channels in eliciting changes (Figs 2, 3, 4, 5, 6; Fig. S1) observed with 200 μM BaCl2, thereby providing a critical line of evidence that the changes observed after the application of 200 μM BaCl2 were specific to the blockade of KA channels.


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

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

Bath application of 50 μM BaCl2 introduced small but significant differences in certain subthreshold measurements at hyperpolarized, but not depolarized, voltages.(a) Schematic showing experimental setup for assessing the effect of bath application of 50 μM BaCl2 on various physiologically relevant measurements at the soma. The experimental protocol was the same as that depicted in Fig. 1a, with the only difference being the reduction in the concentration of BaCl2 from 200 μM to 50 μM. (b) Voltage response of an example cell to constant current injection for 700 ms of varying amplitude, from −50 to +50 pA in steps of 10 pA, under baseline condition (blue) and after application of 50 μM BaCl2 (orange). (c) Top, voltage traces in response to a train of five α-EPSCs at 20 Hz under baseline condition (blue) and after application of 50 μM BaCl2 (orange). Voltage traces, in response to a pulse current of 200 pA for 700 ms, recorded from the soma under baseline condition (blue) and after application of 50 μM BaCl2 (orange). (d) Voltage traces recorded from the soma in response to the Chirp15 stimulus under baseline condition (blue) and after application of 50 μM BaCl2 (orange). All traces in (b–d) were recorded from the same neuron. (e,f) Impedance amplitude (e) and phase (f) plotted as functions of input current frequency derived from corresponding color-matched traces shown in (d). (g–o) Population data (n = 8; mean ± SEM) for the effect of applying 50 μM BaCl2 on input resistance (g); input resistance (h) and sag ratio (i) as functions of voltage; temporal summation strength (j); action potential firing frequency for different current injections (k); and resonance frequency (l), total inductive phase (m), resonance strength (n) and maximal impedance amplitude (o) as functions of voltage. For (g–o), *p < 0.05 for paired Student’s t test, baseline measurements are depicted in blue and measurements obtained after application of 50 μM BaCl2 are plotted in orange.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4837398&req=5

f7: Bath application of 50 μM BaCl2 introduced small but significant differences in certain subthreshold measurements at hyperpolarized, but not depolarized, voltages.(a) Schematic showing experimental setup for assessing the effect of bath application of 50 μM BaCl2 on various physiologically relevant measurements at the soma. The experimental protocol was the same as that depicted in Fig. 1a, with the only difference being the reduction in the concentration of BaCl2 from 200 μM to 50 μM. (b) Voltage response of an example cell to constant current injection for 700 ms of varying amplitude, from −50 to +50 pA in steps of 10 pA, under baseline condition (blue) and after application of 50 μM BaCl2 (orange). (c) Top, voltage traces in response to a train of five α-EPSCs at 20 Hz under baseline condition (blue) and after application of 50 μM BaCl2 (orange). Voltage traces, in response to a pulse current of 200 pA for 700 ms, recorded from the soma under baseline condition (blue) and after application of 50 μM BaCl2 (orange). (d) Voltage traces recorded from the soma in response to the Chirp15 stimulus under baseline condition (blue) and after application of 50 μM BaCl2 (orange). All traces in (b–d) were recorded from the same neuron. (e,f) Impedance amplitude (e) and phase (f) plotted as functions of input current frequency derived from corresponding color-matched traces shown in (d). (g–o) Population data (n = 8; mean ± SEM) for the effect of applying 50 μM BaCl2 on input resistance (g); input resistance (h) and sag ratio (i) as functions of voltage; temporal summation strength (j); action potential firing frequency for different current injections (k); and resonance frequency (l), total inductive phase (m), resonance strength (n) and maximal impedance amplitude (o) as functions of voltage. For (g–o), *p < 0.05 for paired Student’s t test, baseline measurements are depicted in blue and measurements obtained after application of 50 μM BaCl2 are plotted in orange.
Mentions: BaCl2 is an established blocker of certain types of inward-rectifying potassium (KIR) channels2627 at lower concentrations (50 μM). This implies that KIR channels were also blocked in our experiments with BaCl2, where we had employed BaCl2 at 200 μM to block KA channels22. What was the contribution of KIR channels to the changes (Figs 2, 3, 4, 5, 6, Fig. S1) in intrinsic excitability, spectral selectivity and phase tuning observed with BaCl2 as the pharmacological agent? Could the voltage-dependence of intrinsic measurements be explained with blockade of KIR channels? To answer these questions directly, we measured changes in intrinsic properties before and after application of 50 μM BaCl2, a concentration where BaCl2-induced blockade of KIR channels is more efficacious than that of KA channels. We found that 50 μM BaCl2 was insufficient to elicit significant differences in Rin, firing frequency or temporal summation (Fig. 7b,c,g,j,k). Additionally, when we assessed intrinsic measurements as functions of membrane voltage, in striking contrast to our results with 200 μM BaCl2 (Fig. 6, Fig. S1), we found that 50 μM BaCl2 was insufficient to introduce significant changes in any of the measurements at depolarized potentials (Fig. 7h,i,k–o). Significant effects of applying 50 μM BaCl2 were confined to measurements at hyperpolarized voltages, specifically in (Fig. 7h), fR (Fig. 7l) and /Z/max (Fig. 7o), thereby ruling out a role for KIR channels in introducing significant changes observed in depolarizing potentials (with 200 μM BaCl2). Together, these results argue against a significant role for KIR channels in eliciting changes (Figs 2, 3, 4, 5, 6; Fig. S1) observed with 200 μM BaCl2, thereby providing a critical line of evidence that the changes observed after the application of 200 μM BaCl2 were specific to the blockade of KA channels.

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