Axons are inherently noisy due to the spontaneous openings and closings of ion channels that cause membrane potential fluctuations. When the noise becomes too great, a spontaneous action potential ensues, which can disrupt communication between axons. As the rate of this spontaneous firing increases exponentially as axon diameter decreases, Faisal wondered whether channel noise limits axon size.
To test this question, the team developed a mathematical model that tracks axon dynamics when single ion channels “behave badly,” or open and close at the maximum threshold observed experimentally. Using data from well-studied biological systems, such as specialized cortical rodent and squid axons, they found that axon diameter is the most significant factor affecting spontaneous action potentials; other factors such as channel density, channel conductance, and membrane properties had little effect.
Although the necessary molecular machinery can be packaged into an axon only 0.06 μm in diameter, the model predicted that axon size must be at least 0.10 μm. Below this size, spontaneous axon firing is so prevalent that effective communication between axons becomes garbled. Indeed, the smallest natural axons that they found were 0.10 μm in diameter, with a few unusual exceptions.
The mechanism driving action potentials is one of the best-studied cellular signaling systems, but “it is not well-appreciated that these biological systems are not perfectly reliable,” says Faisal. Recognizing that noise is inherent in biological signaling systems at the nanometer scale is important both for studying cells and for applying nanotechnology founded on similar biomolecular mechanisms.