麩胺酸是負責脊椎動物大腦中樞神經系統中主要的興奮性神經傳導物質之一。離子通道型麩胺酸受器依其藥理學特性可分為三種次型，分別是AMPA、kainate及NMDA受器。AMPA受器負責脊椎動物中樞神經系統中快速的興奮性神經傳導。Gria1為有顎動物四種AMPA受器單元之一，吳郭魚表現二種來自複製的Gria1基因。脊椎動物每一AMPA受器可有二種splice型式，稱為flip及flop型式，flip型式通常活性較flop型式好。不同於哺乳動物AMPA受器單元，以AMPA受器促效劑刺激吳郭魚Gria1□i (i表示為flip isoform) 時偵測不到離子通道活性，需添加減緩AMPA受器去敏感化作用 (desensitization) 的CTZ (cyclothiazide)才能偵測到促效劑誘發電流。Gria1□□ ( flop isoform)單獨以促效劑刺激即可偵測到誘發電流的產生，顯示吳郭魚Gria1□ flop型式受器活性較flip好。flip及flop型式單元的氨基酸序列的差異在於最後一個穿膜區前的38個氨基酸。比對吳郭魚Gria1□i與其他有硬骨魚及哺乳類的Gria1的flip序列，發現吳郭魚Gria1□i有四個特有的氨基酸與哺乳類不同。我們對flip區域四個氨基酸進行點突變，證實I740 胺基酸參與調控受器的去敏感化速率。N750胺基酸影響CTZ增加受器對kainate親和性及減緩麩胺酸誘發去敏感化作用的能力。I740、A753及R776胺基酸會增加麩胺酸誘發電流相對於kainate誘發電流的比例。Gria1□i與另一個AMPA受器次單元Gria2βi一起表現於爪蟾卵母細胞，由電流表現變大及誘發電流與膜電位呈現直線關係的結果證明Gria1□i能與其他AMPA受器組成具有功能的異構型受器。
吳郭魚AMPA受器Gria1β C端與p22蛋白質在酵母菌雙雜合系統中有交互作用。為瞭解p22對AMPA受器的影響，我們將p22與帶有Gria1β C端的Gria3αi (3□i/1βC21) 在爪蟾卵母細胞中共同表現。p22可降低3αi/1βC21離子通道麩胺酸相對於kainate的誘發電流比。p22對3αi/1βC21所造成的影響可受CTZ抑制，顯示由p22所造成的影響是透過加速3αi/1βC21之去敏感化作用。

L-glutamate is the major excitatory neurotransmitter in the vertebrate central nervous system. Ionotropic glutamate receptors are divided into three subtypes, AMPA-, kainate- and NMDA-preferring receptors. AMPA receptors mediate fast excitatory neurotransmission in the vertebrate central nervous system. Oreochomis mossambicus (tilapia) expresses two duplicated Gria1 genes. All vertebrate AMPA receptor genes are alternatively spliced to create two isoforms, flip and flop. In general, AMPA receptors comprising the flip isoform are more active than those comprising the flop isoform. The agonist-activated activities of Gria1□i, i represents the flip isoform, were only detected in the presence of the desensitization attenuator, cyclothiazide. On the other hand, channel activities of Gria1αo, o represents the flop isoform, could be detected in the absence of cyclothiazide, implying that channel of Gria1αo was more active than that of Gria1□i. The Gria1αi and Gria1αo differed only in the 38-amino acid flip/flop region in front of the last transmembrane region. The flip sequence of tilapia Gria1□ differed from that of mammalian Gria1 in four positions, which were individually mutated in this report to study their roles in controlling the tilapia Gria1□ channel properties. Electrophysiological analyses showed that I740 residue is responsible for fast desensitization in the Gria1□i. Substitution of a serine at position 750 increased the binding affinity of kainate, and attenuated the desensitization evoked by glutamate in the presence of cyclothiazide. I740, A753 and R776 residues are responsible for the higher ratio of the glutamate-activated currents over the kainate-activated currents in the Gria1αi. The activated currents recorded from Xenopus oocytes coinjected with Gria1αi and Gria2βi were larger than that from oocytes injected with Gria1αi or Gria2βi only. Furthermore, the glutamate-activated currents in the Gria1αi and Gria2βi coexpressed oocytes displayed a linear current-voltage relationship. These results demonstrated that Gria1αi and Gria2βi can form functional heteromeric receptors.
Gria1β C-terminal region can interact with p22 in the yeast two-hybrid system and it coprecipitates with p22 in cells coexpressed both proteins. To study the physiological functions of the interaction between p22 and Gria1β C-terminal region, p22 and chimera 3αi/1βC21, which consisted of the Gria3α backbone with the Gria1β C-terminal region, were coexpressed in Xenopus oocytes. The ratio of glutamate-activated currents over the kainate-activated currents recorded in 3αi/1βC21 decreased by coexpressing p22. Addition of cyclothiazide rescued the p22 effects on 3αi/1βC21, suggesting that p22 was involved in increasing the desensitization of 3αi/1βC21 receptor.

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