State and location dependence of action potential metabolic cost in cortical pyramidal neurons

Abstract

Action potential generation and conduction requires large quantities of energy to restore Na(+) and K(+) ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na(+)/K(+) charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.

Neuronal energy consumption: biophysics, efficiency and evolution

“…This is not, however, their sole function; action potentials are also important for preventing noise accumulation in successive layers of information processing in neural circuits. The energy consumption of a single action potential within a single neuron would be challenging to measure directly, so typically it is estimated by converting the electrical signals into the total amount of work the 3Na + /2K + pump must do to restore ion gradients (Box 1) [9,[25][26][27][28][29][30][31][32][33][34][35][36]. Estimates of action potential energy consumption are, consequently, dependent upon accurate measurement of biophysical parameters including channel kinetics, conductance magnitudes and membrane capacitances.…”

“…It was assumed that the energy consumption of this action was broadly representative of other action potentials [9]; however, this was dispelled by combining experimental measurements and computational modelling of a range of action potentials primarily from mammalian neurons [26][27][28][29]. This demonstrated that the squid giant axon action potential was profligate in its energy consumption compared to most other action potentials, and revealed a hitherto unappreciated heterogeneity in the biophysics of the currents generating action potentials and their consequences for the energy consumption of the action potential [25][26][27][28][29][30][31][32][33][34][35][36]. The major cause of differences in energy consumption was identified as the overlap between the inward and outward currents during the action potential [26,28,34,35]: A large overlap inflates energy consumption whereas complete separation of the currents reduces energy consumption close to the minimum possible.…”

A Specific and Essential Role for Na,K-ATPase α3 in Neurons Co-expressing α1 and α3

“…To mimic this situation of suprathreshold neuronal activity, Na ϩ recordings were performed in dendrites following a transient large increase in [Na ϩ ] i . The energy cost for turn-over of Na,K-ATPase is estimated to be ϳ50% of total brain energy consumption (16) and because sev-eral lines of evidence suggest that the majority of this Na ϩ current dependent energy is expended postsynaptically rather than presynaptically (17), the Na ϩ imaging studies were performed on dendrites.…”

The energetics of electric organ discharge generation in gymnotiform weakly electric fish

“…From the total Na + flux during an action potential in both somatic and axonic compartments, and using standard methods (e.g. Alle et al, 2009;Sengupta et al, 2010), we calculate the cost of a single action potential in a P neuron to be about 10 9 ATP molecules (Fig.4C); this is similar to, but on the high end of the range of, previous estimates for other neurons (Attwell and Laughlin, 2001;Lennie, 2003;Hallermann et al, 2012). Note that such estimates depend strongly on the relative gating kinetics of the Na + and K + channels and can vary significantly between neurons (Sengupta et al, 2010).…”

“…Alle et al, 2009;Sengupta et al, 2010). Such estimates suggest that each action potential consumes between 10 7 and 10 9 ATP molecules depending on neuron type (Attwell and Laughlin, 2001;Lennie, 2003;Sengupta et al, 2010;Hallermann et al, 2012;. Thus, an action potential in just a single neuron can consume an order of magnitude more energy than the minimal amount required to assemble the electric field, suggesting that the actual cost of EOD generation must be several orders of magnitude higher than this theoretical lower bound.…”