Contini Donatella, Price Steven D, Art Jonathan J
Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA.
J Physiol. 2017 Feb 1;595(3):777-803. doi: 10.1113/JP273060. Epub 2016 Nov 4.
In the synaptic cleft between type I hair cells and calyceal afferents, K ions accumulate as a function of activity, dynamically altering the driving force and permeation through ion channels facing the synaptic cleft. High-fidelity synaptic transmission is possible due to large conductances that minimize hair cell and afferent time constants in the presence of significant membrane capacitance. Elevated potassium maintains hair cells near a potential where transduction currents are sufficient to depolarize them to voltages necessary for calcium influx and synaptic vesicle fusion. Elevated potassium depolarizes the postsynaptic afferent by altering ion permeation through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, and contributes to depolarizing the afferent to potentials where a single EPSP (quantum) can generate an action potential. With increased stimulation, hair cell depolarization increases the frequency of quanta released, elevates [K ] and depolarizes the afferent to potentials at which smaller and smaller EPSPs would be sufficient to trigger APs.
Fast neurotransmitters act in conjunction with slower modulatory effectors that accumulate in restricted synaptic spaces found at giant synapses such as the calyceal endings in the auditory and vestibular systems. Here, we used dual patch-clamp recordings from turtle vestibular hair cells and their afferent neurons to show that potassium ions accumulating in the synaptic cleft modulated membrane potentials and extended the range of information transfer. High-fidelity synaptic transmission was possible due to large conductances that minimized hair cell and afferent time constants in the presence of significant membrane capacitance. Increased potassium concentration in the cleft maintained the hair cell near potentials that promoted the influx of calcium necessary for synaptic vesicle fusion. The elevated potassium concentration also depolarized the postsynaptic neuron by altering ion permeation through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. This depolarization enabled the afferent to reliably generate action potentials evoked by single AMPA-dependent EPSPs. Depolarization of the postsynaptic afferent could also elevate potassium in the synaptic cleft, and would depolarize other hair cells enveloped by the same neuritic process increasing the fidelity of neurotransmission at those synapses as well. Collectively, these data demonstrate that neuronal activity gives rise to potassium accumulation, and suggest that potassium ion action on HCN channels can modulate neurotransmission, preserving the fidelity of high-speed synaptic transmission by dynamically shifting the resting potentials of both presynaptic and postsynaptic cells.
在I型毛细胞与杯状传入神经之间的突触间隙中，钾离子会随着活动而积累，动态改变驱动力以及通过面向突触间隙的离子通道的通透性。由于存在较大的电导，在存在显著膜电容的情况下可将毛细胞和传入神经的时间常数降至最低，从而实现高保真突触传递。升高的钾离子使毛细胞维持在一个电位附近，此时转导电流足以将它们去极化到钙内流和突触小泡融合所需的电压。升高的钾离子通过改变超极化激活的环核苷酸门控（HCN）通道的离子通透性使突触后传入神经去极化，并有助于将传入神经去极化到单个兴奋性突触后电位（量子）即可产生动作电位的电位。随着刺激增加，毛细胞去极化增加量子释放频率，升高[K⁺]并将传入神经去极化到越来越小的兴奋性突触后电位就足以触发动作电位的电位。
快速神经递质与较慢的调节效应器共同作用，这些调节效应器在巨大突触（如听觉和前庭系统中的杯状末梢）中受限的突触空间中积累。在这里，我们使用乌龟前庭毛细胞及其传入神经元的双膜片钳记录来表明，在突触间隙中积累的钾离子调节膜电位并扩展了信息传递范围。由于存在较大的电导，在存在显著膜电容的情况下可将毛细胞和传入神经的时间常数降至最低，从而实现高保真突触传递。突触间隙中钾离子浓度的增加使毛细胞维持在促进突触小泡融合所需的钙内流的电位附近。升高的钾离子浓度还通过改变超极化激活的环核苷酸门控（HCN）通道的离子通透性使突触后神经元去极化。这种去极化使传入神经能够可靠地产生由单个AMPA依赖性兴奋性突触后电位诱发的动作电位。突触后传入神经的去极化还可使突触间隙中的钾离子升高，并使被同一神经突过程包裹的其他毛细胞去极化，从而也提高了这些突触处神经传递的保真度。总体而言，这些数据表明神经元活动会导致钾离子积累，并表明钾离子对HCN通道的作用可调节神经传递，通过动态改变突触前和突触后细胞的静息电位来保持高速突触传递的保真度。
