Ionic basis of neuronal bistability

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Bistability is a striking phenomenon found in various systems in which two very different behaviors can occur for the same external conditions. For example, new-born infants can suddenly stop breathing - for unknown reasons - a condition known as apnea, and, several seconds later, resume normal breathing for reasons which are also unknown. Bistability is also found in simpler systems, including squid giant axons. When the pH of the intracellular medium of the axon is elevated to 7.7, or higher, the axon is either quiescent or spontaneously firing action potentials in a rhythmic manner at a rate of approximately 25 Hz. The spontaneous firing can last for several hours. The ion channel mechanisms underlying this behavior are a persistent, tetrodotoxin-sensitive sodium ion channel, INaP, and a acid-sensing-ion-channel (ASIC) which is also sodium selective. This ASIC differs from the ASIC's found in the mammalian nervous system in that the H+ sensitivity is on the inner surface of the membrane. Alkalinization of the intracellular milleau turns off the ASIC, thereby allowing the INaP channel to destabilize the normal rest state of the axon. We have examined transitions between the two stable states in alkalinized axons, repetitive firing and quiescence, by injecting computer generated noise into the axon. The pattern of on-off switching of the pacemaker depends upon the intensity, spectral properties, and phase angle of the noise stimulus current. Our results reveal a distinct form of bistability in which noise can either silence pacemaker activity, trigger repetitive firing, or induce sporadic burst patterns similar to those recorded in a variety of normal and pathological neurons.