Channeling the Central Dogma

Abstract

How do neurons and networks achieve their characteristic electrical activity, regulate this activity homeostatically, and yet show population variability in expression? In this issue of Neuron, O'Leary et al. (2014) address some of these thorny questions in this theoretical analysis that starts with the Central Dogma.

Figure 1

Channeling the Central Dogma. A. A simple biochemical scheme for activity-dependent ion channel expression. Channel mRNAs are synthesized at a channel-specific rate,α_mi, that depends on a Ca²⁺-activated universal transcription factor, T, and are degraded at rate,β_mi. Functional channel proteins are produced at a uniform rate,α_g,from mRNAs and degraded at a uniform rate,β_g. B. Examples of two cell types produced from the same set of seven voltage-dependent channel types (indicated below as g_i's: g_Na, fast sodium; g_CaS, slow Ca; g_CaT, transient Ca; g_KA, A-type/transient potassium; g_KCa, Ca-dependent potassium; g_Kdr, delayed-rectifier potassium; g_H, hyperpolarization-activated mixed-cation). Left-hand plots: log-log plots of maximal conductance (ḡ) evolution over time. Each example has a different set of regulation time-constants (τ_mi's) for the conductances. Total duration for all simulations is 10 * τ_g. Right-hand plots: membrane potential traces with current injection traces (-500 pA) shown below. C. Scatter plots of steady-state maximal conductances in each cell type shown in B after 20 independent runs. Straight lines are calculated from the ratio of regulation time-constants for each pair of conductances in each cell type. Adapted from O'Leary et al. (2014).