Ionic basis of neuronal bistability

双稳态是一种在各种系统中发现的引人注目的现象，其中两种非常不同的行为可以在相同的外部条件下发生。例如，新生儿可能会突然停止呼吸-原因不明-一种称为呼吸暂停的情况，几秒钟后，由于未知的原因恢复正常呼吸。双稳性也存在于更简单的系统中，包括鱿鱼的巨大轴突。当轴突的细胞内介质的pH为 升高到7.7或更高，轴突是静止的或以约25 Hz的速率以节律的方式自发地激发动作电位。自发放电可以持续几个小时。这种行为背后的离子通道机制是持续的河豚毒素敏感性钠离子通道INaP和也是钠选择性的酸敏感离子通道（ASIC）。这种ASIC与在哺乳动物神经系统中发现的ASIC的不同之处在于H+敏感性在膜的内表面上。细胞内milleau的碱化关闭ASIC，从而允许INaP通道破坏轴突的正常静息状态。我们已经研究了碱化轴突，重复放电和静止，通过注入计算机产生的噪音到轴突的两个稳定状态之间的转换。起搏器的开关模式取决于噪声刺激电流的强度、频谱特性和相位角。我们的研究结果揭示了一种独特的双稳态形式，其中噪声可以沉默起搏器活动，触发重复放电，或诱导类似于在各种正常和病理神经元中记录的零星突发模式。

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.