Document Detail

Inactivating ion channels augment robustness of subthreshold intrinsic response dynamics to parametric variability in hippocampal model neurons.
MedLine Citation:
PMID:  22930270     Owner:  NLM     Status:  MEDLINE    
Voltage-gated ion channels play a critical role in regulating neuronal intrinsic response dynamics (IRD). Here, we computationally analysed the roles of the two inactivating subthreshold conductances (A and T), individually and in various combinations with the non-inactivating h conductance, in regulating several physiological IRD measurements in the theta frequency range. We found that the independent presence of a T conductance, unlike that of an h conductance, was unable to sustain an inductive phase lead in the theta frequency range, despite its ability to mediate theta frequency resonance. The A conductance, on the other hand, when expressed independently, acted in a manner similar to a leak conductance with reference to most IRD measurements. Next, analysing the impact of pair-wise coexpression of these channels, we found that the coexpression of the h and T conductances augmented the range of parameters over which they sustained resonance and inductive phase lead. Additionally, coexpression of the A conductance with the h or the T conductance elicited changes in IRD measurements that were similar to those obtained with the expression of a leak conductance with a resonating conductance. Finally, to understand the global sensitivity of IRD measurements to all parameters associated with models expressing all three channels, we generated 100,000 neuronal models, each built with a unique set of parametric values. We categorized valid models among these by matching their IRD measurements with experimental counterparts, and found that functionally similar models could be achieved even when underlying parameters displayed tremendous variability and exhibited weak pair-wise correlations. Our results suggest that the three prominent subthreshold conductances contribute differently to intrinsic excitability and to phase coding. We postulate that the differential expression and activity-dependent plasticity of these conductances contribute to robustness of subthreshold IRD, whereby response homeostasis is achieved by recruiting several non-unique combinations of these channel parameters.
Rahul Kumar Rathour; Rishikesh Narayanan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-28
Journal Detail:
Title:  The Journal of physiology     Volume:  590     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-16     Completed Date:  2013-05-01     Revised Date:  2013-12-05    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  5629-52     Citation Subset:  IM    
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MeSH Terms
Action Potentials
Calcium / metabolism
Calcium Channels, T-Type / physiology*
Models, Neurological*
Potassium / metabolism
Potassium Channels, Voltage-Gated / physiology*
Pyramidal Cells / physiology*
Rats, Sprague-Dawley
Reg. No./Substance:
0/Calcium Channels, T-Type; 0/Potassium Channels, Voltage-Gated; RWP5GA015D/Potassium; SY7Q814VUP/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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