Repository logo
 

Activity-dependent compensation of cell size is vulnerable to targeted deletion of ion channels.

Published version
Peer-reviewed

Change log

Authors

Gorur-Shandilya, Srinivas 
Marder, Eve 

Abstract

In many species, excitable cells preserve their physiological properties despite significant variation in physical size across time and in a population. For example, neurons in crustacean central pattern generators generate similar firing patterns despite several-fold increases in size between juveniles and adults. This presents a biophysical problem because the electrical properties of cells are highly sensitive to membrane area and channel density. It is not known whether specific mechanisms exist to sense membrane area and adjust channel expression to keep a consistent channel density, or whether regulation mechanisms that sense activity alone are capable of compensating cell size. We show that destabilising effects of growth can be specifically compensated by feedback mechanism that senses average calcium influx and jointly regulate multiple conductances. However, we further show that this class of growth-compensating regulation schemes is necessarily sensitive to perturbations that alter the expression of subsets of ion channel types. Targeted perturbations of specific ion channels can trigger a pathological response of the regulation mechanism and a failure of homeostasis. Our findings suggest that physiological regulation mechanisms that confer robustness to growth may be specifically vulnerable to deletions or mutations that affect subsets of ion channels.

Description

Keywords

Animals, Arthropod Proteins, Cell Size, Crustacea, Feedback, Physiological, Gene Deletion, Homeostasis, Ion Channels, Models, Theoretical, Neurons

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

10

Publisher

Springer Science and Business Media LLC
Sponsorship
European Research Council (716643)