Connors B W, Ransom B R
J Physiol. 1984 Oct;355:619-33. doi: 10.1113/jphysiol.1984.sp015442.
The excitability of developing rat optic nerves has been studied under conditions in which extracellular Cl- was replaced with other anions. In nerves younger than 3 days old, replacing Cl- with propionate or SO4(2-) usually led to spontaneous and repetitive cycling of extracellular K+ concentration ([K+]o). [K+]o reached peaks of 8-12 mM and then fell transiently below the base-line level of 5 mM before increasing again. This cycling behaviour continued, with a wave-length of 1-2 min, for as long as 2 h. Nerves older than 5 days either did not cycle or did so only transiently. Substitution of ten different anions for Cl- indicated that a minimum hydrated radius, between that of BrO3- and HCO3-, was necessary to induce cycling behaviour. Cycling behaviour was abolished by the Na+-channel blocker tetrodotoxin. Reduction of the bath [K+] to 2.5 mM slowed the frequency of spontaneous cycles; a bath [K+] of 1 mM abolished them. When the temperature was lowered, cycle frequency slowed. Substitution of large anions for Cl- enhanced axonal excitability. This was inferred from the prevalence of spontaneous action potentials during cycling behaviour, and from the generation of relatively large evoked increases of [K+]o. Cycling behaviour is hypothesized to result from a repetition of the following three processes: (i) spontaneous axonal firing elicits a gradual increase in [K+]o which increases axonal excitability and facilitates further K+ release, (ii) axonal firing and K+ release are eventually halted by a combination of depolarization block, intracellular Na+ accumulation and hyperpolarization from electrogenic pumping, (iii) recovery of [K+]o to its minimal value depends on active K+ reuptake mediated by a highly stimulated axonal Na+-K+-ATPase. We conclude that a large proportion of the resting membrane conductance of optic nerve fibres is Cl- specific. A high Cl- conductance may stabilize fine central axons against the depolarizing effects of [K+]o increases.
在将细胞外氯离子用其他阴离子替代的条件下，对发育中的大鼠视神经兴奋性进行了研究。在小于3日龄的神经中，用丙酸盐或硫酸根（SO4(2-)）替代氯离子通常会导致细胞外钾离子浓度（[K+]o）自发且重复地循环变化。[K+]o达到8 - 12 mM的峰值，然后短暂降至5 mM的基线水平以下，之后再次升高。这种循环行为持续存在，波长为1 - 2分钟，长达2小时。5日龄以上的神经要么不发生循环，要么仅短暂循环。用十种不同阴离子替代氯离子表明，诱导循环行为需要介于溴酸根离子和碳酸氢根离子之间的最小水合半径。钠离子通道阻滞剂河豚毒素可消除循环行为。将浴槽中[K+]降至2.5 mM会减慢自发循环的频率；浴槽中[K+]为1 mM时则会消除循环。当温度降低时，循环频率减慢。用大阴离子替代氯离子可增强轴突兴奋性。这是从循环行为期间自发动作电位的普遍存在以及相对较大的诱发[K+]o升高的产生推断出来的。推测循环行为是由以下三个过程的重复导致的：（i）自发的轴突放电引发[K+]o逐渐升高，这会增加轴突兴奋性并促进进一步的钾离子释放，（ii）轴突放电和钾离子释放最终因去极化阻滞、细胞内钠离子积累以及电生泵引起的超极化的共同作用而停止，（iii）[K+]o恢复到其最小值取决于由高度刺激的轴突钠钾ATP酶介导的主动钾离子再摄取。我们得出结论，视神经纤维静息膜电导的很大一部分是氯离子特异性的。高氯离子电导可能使中枢细轴突稳定，抵抗[K+]o升高的去极化作用。
