The cost of an action potential.
Neuronal modules, or 'cell-assemblies', comprising millions of mutually interconnected cells have been postulated to form the basis of many functions of the brain, such as mood, sleep, hunger, vigilance, and more. Depending on the extent of the module, neurocommunication in cell-assemblies might exceed metabolic resources. A medium-size (10000 neurons) module would require at least 10 J per l of brain, based on a calculated cost of an isolated action potential (AP) of 10(11)-10(12) molecules of ATP per cm(2) of cell membrane, with an absolute minimum of 10(6) ATP at a node of Ranvier. The figure matches the cost of depolarizing the unmyelinated axon of the large monopolar cell in the blowfly retina. A circuit model of the cell membrane, based on abrupt changes of Na(+) and K(+) conductances, is used to emulate the AP and to assess the resulting ionic unbalance. The cost of an AP is equated to the metabolic energy necessary to fuel ATP-based pumps that restore intracellular K(+). The high metabolic demand of a cell-assembly suggests that less expensive means of neurocommunication may be involved, such as non-synaptic diffusion neurotransmission (NDN), which would comply with a proposed law of conservation of space and energy in the brain.