The action potential and all its complex properties can be explained by time- and voltage-dependent changes in the Na⁺ and K⁺ permeabilities of neuronal membranes. This conclusion derives primarily from evidence obtained by a device called the voltage clamp. The voltage clamp technique is an electronic feedback method that allows control of neuronal membrane potential and, simultaneously, direct measurement of the voltage-dependent fluxes of Na⁺ and K⁺ that produce the action potential. Voltage clamp experiments show that a transient rise in Na⁺ conductance activates rapidly and then inactivates during a sustained depolarization of the membrane potential. Such experiments also demonstrate a rise in K⁺ conductance that activates in a delayed fashion and, in contrast to the Na⁺ conductance, does not inactivate. Mathematical modeling of the properties of these conductances indicates that they, and they alone, are responsible for the production of all-or-none action potentials in the squid axon. Action potentials propagate along the nerve cell axons, initiated by the voltage gradient between the active and inactive regions of the axon by virtue of the local current flow. In this way, action potentials compensate for the relatively poor passive electrical properties of nerve cells and enable neural signaling over long distances. The molecular underpinnings of these signaling mechanisms will be revealed in the next chapter, which describes the properties of ion channels and transporters.