| On the membrane of neurons, ion channels take important part in formingchemical equilibrium potential，transferring electrical signal，and recovering the restpotential. These ion channels can be classified into three categories: voltage gated ionchannel, metabolic gaed channel and passive ion channel.As one of the important voltage gated ion channels, inward rectifier potassiumchannels (Kir) widely distribute in the cells of neurons and muscle cells. Because whenthe neurons are at rest, the open ion channels are mainly Kirs, Kirs play an importantrole in maintaining the resting potential. If Kir has a pathological change, thecorresponding organ will lose its function. So it’s necessary to study Kir both inphysiology and pathology. Another significant metabolic gated channel, AMPA,plays an important role in conducting the excitable synaptic signal, inducing andmaintaining the long-term potentiation\depression, and modulating study and memory.On the membranes of vertebrate retinal horizontal cells，both Kir and AMPA channelsare expressed.As an important endogenous modulatory factor of nervous system, Zn2+isabundant in the terminal of photoreceptors’ axons and can be released into the synapticgap between photoreceptor cells and horizontal cells with glutamate. Horizontal cellsaccept the glutamatic stimulating of photoreceptor and transfer the electrical signal tothe neurons of next level, and in the meantime, Zn2+released with glutamate canmodulate the ion channels on horizontal cells. This study focuses on the modulation ofZn2+on Kir and AMPA channel.It has been reported that Zn2+can inhibit Kir current at specific pH, but theunderlying mechanism of this phenomenon is not clear. In this study we built a modelwith NEURON software to simulate the relationship of Kir current and voltage. Afterthat, we built a kinetic scheme to describe the inhibition effect of Zn2+on Kir. Thesimulating results show that this model can describe the inhibition effect well, provingthe hypothesis that Zn2+can inhibit Kir by binding to specific site on Kir, and H+cancompete to bind to the same site too. By analyzing the Zn2+releasing constant and H+ releasing constant, we found that Zn2+affect Kir from three aspects: to increase theZn2+binding rate, to increase the Zn2+releasing rate, and to decrease the H+releasingrate.The phenomenon that Zn2+inhibits Kir current is the combination of these threeeffects.When modeling the AMPA receptor, researchers found that complete AMPAmodel is so complicated that they suggest to simplify the model without losing keyfeatures. In this paper, we simplified the existing six-state kinetic scheme of AMPA bycutting the desensitization states, and simulating the experimental AMPA current withthe simplified model. The simulating results show that with the decrease ofdesensitization states, simplified model can simulate the AMPA current in demandedaccuracy but losing the ability to describe the point of inflection. So when the accuracyis not highly demanded, we can use the simplified model without desensitization statesto simulate AMPA current in order to improve calculating efficiency.In this paper, we describe the inhibition mechanism of Zn2+on Kir which gives anew way to model Kir; the Kir model, Zn2+inhibition model and AMPA model withoutdesensitization states can be used in network of neurons and related modeling work; theexplanation of inhibition effect of Zn2+on Kir current provides a new idea on Kirstudy. |
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