Pressure wave model for action potential propagation in excitable cells

Speed of propagation of small-amplitude pressure waves through the cytoplasmic interior of myelinated and unmyelinated axons of different diameters is theoretically estimated and is found to generally agree with the action potential (AP) conduction velocities. This remarkable coincidence allows to surmise a model in which AP spread along axon is propelled not by straggling ionic currents as in the widely accepted local circuit theory, but by mechanoactivation of the membrane ion channels by a traveling pressure pulse. Hydraulic pulses propagating in the viscous axoplasm are calculated to decay over ∼ 1 mm distances, and it is further hypothesized that it is the role of influxing during the AP Ca ions to activate membrane skeletal protein network attached to the membrane cytoplasmic side for a brief radial contraction amplifying the pressure pulse and preventing its decay. The model correctly predicts that the AP conduction velocity should vary as the one-half power of axon diameter for large unmyelinated axons, and as the first power of the diameter for myelinated axons, provided that specific mechanical properties of axons are independent from diameter; that myelinization increases the conduction velocity; that the conduction velocity increases with the temperature. Unlike the local circuit theory, the model is able to qualitatively explain observed increase in the AP duration in axons of smaller diameters. Predictions of absolute AP conduction velocities are limited by the knowledge of relevant to propagation of pressure waves mechanical properties of axons, still, the velocities are predicted well for myelinated axons, while an agreement for unmyelinated axons requires 3 orders of magnitude higher resistance of axons to deformation increasing their diameter compared to values deduced from published data on membrane area expansion moduli. The model can be viewed as competing with the local circuit theory for AP propagation, and, if realized in neurons, would imply that pressure-related phenomena could participate in various aspects of neuron function, such as the synaptic vesicle release, synaptic integration, learning and memory. Correspondence to: M. M. Rvachev ( Fax: +1-617-2585440, email: [email protected], after June 2003 [email protected]) The model also suggests a new outlook on the evolution of the signal transmission in cells, a rationale behind mechanosensitivity of many ion channels and a physiological role of axonal calcium influx.