JP3128386B2 - Neural model element - Google Patents
Neural model elementInfo
- Publication number
- JP3128386B2 JP3128386B2 JP05080667A JP8066793A JP3128386B2 JP 3128386 B2 JP3128386 B2 JP 3128386B2 JP 05080667 A JP05080667 A JP 05080667A JP 8066793 A JP8066793 A JP 8066793A JP 3128386 B2 JP3128386 B2 JP 3128386B2
- Authority
- JP
- Japan
- Prior art keywords
- membrane
- lipid
- impregnated
- impregnated membrane
- ion pump
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 230000001537 neural effect Effects 0.000 title description 8
- 239000012528 membrane Substances 0.000 claims description 80
- 108010083687 Ion Pumps Proteins 0.000 claims description 27
- 102000004310 Ion Channels Human genes 0.000 claims description 22
- 239000007864 aqueous solution Substances 0.000 claims description 16
- 210000005036 nerve Anatomy 0.000 claims description 14
- 150000002500 ions Chemical class 0.000 claims description 6
- 230000032258 transport Effects 0.000 claims description 3
- 108010082845 Bacteriorhodopsins Proteins 0.000 claims description 2
- 238000000638 solvent extraction Methods 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 description 17
- 150000002632 lipids Chemical class 0.000 description 11
- 210000004676 purple membrane Anatomy 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 238000010586 diagram Methods 0.000 description 4
- 239000010408 film Substances 0.000 description 4
- 230000010365 information processing Effects 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000004298 light response Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000013011 mating Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000010409 thin film Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229910021607 Silver chloride Inorganic materials 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009056 active transport Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000010355 oscillation Effects 0.000 description 2
- 230000009057 passive transport Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229920002284 Cellulose triacetate Polymers 0.000 description 1
- NNLVGZFZQQXQNW-ADJNRHBOSA-N [(2r,3r,4s,5r,6s)-4,5-diacetyloxy-3-[(2s,3r,4s,5r,6r)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6s)-4,5,6-triacetyloxy-2-(acetyloxymethyl)oxan-3-yl]oxyoxan-2-yl]methyl acetate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](OC(C)=O)[C@H]1OC(C)=O)O[C@H]1[C@@H]([C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](COC(C)=O)O1)OC(C)=O)COC(=O)C)[C@@H]1[C@@H](COC(C)=O)O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O NNLVGZFZQQXQNW-ADJNRHBOSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 230000037427 ion transport Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- -1 polytetrafluoroethylene Polymers 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
Landscapes
- Photometry And Measurement Of Optical Pulse Characteristics (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、生物の神経細胞での電
気振動信号による情報伝達の要素となる非線形振動信号
を発生する神経モデル素子に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a nerve model element for generating a non-linear vibration signal which is an element of information transmission by an electric vibration signal in a biological nerve cell.
【０００２】[0002]
【従来の技術】生体内における情報処理では、神経系の
発火が情報伝達の源であり、それは生体膜におけるタン
パク質の機能によって発生する振動と考えられている。
その振動信号は外部刺激に対し様々な変化対応を示し、
神経中枢へその刺激情報を伝達する。2. Description of the Related Art In information processing in a living body, firing of the nervous system is a source of information transmission, which is considered to be vibration generated by the function of a protein in a biological membrane.
The vibration signal shows various changes in response to external stimuli,
The stimulus information is transmitted to the nerve center.
【０００３】有機材料を用いて人工的にこの振動を得る
手段として、水溶液中の脂質薄膜から振動信号を得るモ
デルがある。これは、脂質分子のゆらぎにより発生する
電気振動である（例えば、吉川，表面 第２６巻 第１
１号（１９８８）または都甲，山藤，膜 第１２巻 第
１号（１９８７）参照）。As a means for artificially obtaining this vibration using an organic material, there is a model for obtaining a vibration signal from a lipid thin film in an aqueous solution. This is electric vibration generated by fluctuation of lipid molecules (for example, Yoshikawa, Surface, Vol. 26, No. 1)
No. 1 (1988) or Toko, Yamafuji, Membrane Vol. 12, No. 1 (1987)).
【０００４】[0004]
【発明が解決しようとする課題】しかしながら、この振
動では膜中にあってこの振動を発生させているタンパク
質の存在が考慮されていない。従って、外部からの入力
によって特定モードの振動を発生させること、即ち、振
動を制御することは困難となり、神経をモデル化した素
子とは言い難い。However, this vibration does not take into account the presence of proteins that are present in the membrane and generate this vibration. Therefore, it is difficult to generate a vibration in a specific mode by an external input, that is, it is difficult to control the vibration, and it is hard to say that the element is a nerve modeled element.
【０００５】本発明は、脂質薄膜を基本構造とし、その
膜内に種々のイオンを輸送あるいは通過させるタンパク
質あるいはポリペプチドを配置した生体膜モデルで、光
照射あるいは化学物質などの外部刺激に対応して様々に
変化する電気振動信号を与える素子を提供することを目
的とする。[0005] The present invention is a biological membrane model having a lipid thin film as a basic structure, and a protein or polypeptide for transporting or passing various ions arranged in the membrane, and which responds to light irradiation or external stimuli such as chemical substances. To provide an element that gives an electric vibration signal that changes in various ways.
【０００６】[0006]
【課題を解決するための手段】上記目的を達成するため
に、本発明に係る神経モデル素子は、容器に貯留された
イオン性水溶液と、前記イオン性水溶液を仕切る脂質含
浸膜であって光照射あるいは基質の添加等の外部刺激に
より作動し前記イオン性水溶液中のイオンを能動輸送す
るイオンポンプ及び該脂質含浸膜の両側の膜電位差があ
る閾値に達することで開くイオンチャネルが埋設されて
いる脂質含浸膜と、前記脂質含浸膜に外部刺激を付与す
る手段と、前記脂質含浸膜の膜電位を電気信号として伝
達する電極と、を含むことを特徴とする。In order to achieve the above object, a neural model element according to the present invention comprises an ionic aqueous solution stored in a container, and a lipid-impregnated membrane for partitioning the ionic aqueous solution, the light being irradiated with light. Alternatively, an ion pump that operates by an external stimulus such as addition of a substrate and actively transports ions in the ionic aqueous solution, and a lipid in which an ion channel that opens when the membrane potential difference on both sides of the lipid-impregnated membrane reaches a certain threshold value It is characterized by including an impregnated membrane, means for applying an external stimulus to the lipid-impregnated membrane, and an electrode for transmitting a membrane potential of the lipid-impregnated membrane as an electric signal.
【０００７】[0007]
【作用】以上のような構成を有する本発明の神経モデル
素子によれば、脂質含浸膜に外部刺激が付与されると、
イオンポンプが作動して前記イオン性水溶液中のイオン
が能動輸送され、この能動輸送により、脂質含浸膜の両
側で電位差が生じる。According to the neural model element of the present invention having the above-described structure, when an external stimulus is applied to the lipid-impregnated membrane,
An ion pump is operated to actively transport ions in the ionic aqueous solution, and this active transport causes a potential difference on both sides of the lipid-impregnated membrane.
【０００８】一方、脂質含浸膜の両側で生じる電位差が
ある程度の大きさになると、これを感知してイオンチャ
ネルが開き、イオンポンプにより能動輸送されたイオン
と同符号のイオンが受動輸送されて脂質含浸膜の両側の
膜電位差が解消される。On the other hand, when the potential difference generated on both sides of the lipid-impregnated membrane becomes large to a certain extent, the ion channel is opened and ions having the same sign as the ions actively transported by the ion pump are passively transported. The membrane potential difference on both sides of the impregnated membrane is eliminated.
【０００９】そして、膜電位差が解消されると、イオン
チャネルが閉じて受動輸送が停止される。受動輸送が停
止されると、イオンポンプの能動輸送により再び膜電位
差が生じ、これが所定の大きさになるとイオンチャネル
が開いて膜電位差が解消される。Then, when the membrane potential difference is eliminated, the ion channel closes and the passive transport stops. When the passive transport is stopped, a membrane potential difference occurs again due to the active transport of the ion pump. When the membrane potential reaches a predetermined size, the ion channel is opened to eliminate the membrane potential difference.
【００１０】このようにして、本発明に係る神経モデル
素子においては、外部刺激を付与することにより、イオ
ンポンプが作動して膜電位差が発生する。そして、膜電
位差の発生により、イオンチャネルの開口（膜電位差の
解消）→イオンチャネルの閉口（膜電位差の発生）→イ
オンチャネルの開口（膜電位差の解消）が繰り返され
る。このようにして、所定のイオンポンプとイオンチャ
ネルとを組み合わせて脂質含浸膜に埋設することによ
り、膜電位差の一定周期の増減現象を得ることができ、
これが電極から電気振動信号として得られる。[0010] Thus, in the nerve model element according to the present invention, by applying an external stimulus, the ion pump operates to generate a membrane potential difference. Then, due to the occurrence of the membrane potential difference, the opening of the ion channel (elimination of the membrane potential difference) → the closing of the ion channel (generation of the membrane potential difference) → the opening of the ion channel (elimination of the membrane potential difference) is repeated. In this way, by combining a predetermined ion pump and an ion channel and embedding in a lipid-impregnated membrane, it is possible to obtain a phenomenon of increasing and decreasing the membrane potential difference in a constant cycle,
This is obtained as an electric vibration signal from the electrode.
【００１１】[0011]
【実施例】図１は、本発明の好適な一実施例に係る神経
モデル素子の構成を示すブロック図である。FIG. 1 is a block diagram showing the configuration of a neural model element according to a preferred embodiment of the present invention.
【００１２】本実施例に係る神経モデル素子は、セル１
１ａ及び１１ｂが一体となって形成されたセル１１を有
しており、セル１１ａ或いは１１ｂは、そのままＸ槽或
いはＹ槽を構成する。セル１１のホールＨには脂質含浸
膜１３を取り付けている。Ｘ槽及びＹ槽はイオン性水溶
液１２を満たしており、従ってこれらは脂質含浸膜１３
により仕切られている。Ｘ槽及びＹ槽にはイオン性水溶
液１２は、スターラーバー（撹拌子）Ｑにより撹拌す
る。The neural model element according to the present embodiment is a cell 1
The cell 11a or 11b has a cell 11 integrally formed, and the cell 11a or 11b directly constitutes an X tank or a Y tank. The lipid-impregnated membrane 13 is attached to the hole H of the cell 11. The X and Y tanks are filled with the ionic aqueous solution 12 and therefore they are
Is divided by In the X tank and the Y tank, the ionic aqueous solution 12 is stirred by a stir bar (stir bar) Q.
【００１３】本実施例に係る神経モデル素子は、更に、
脂質含浸膜１３に光照射を行えるように、光源１４及び
ライトガイド１４ａを備えている。光源１４から照射さ
れる光は、ライトガイド１４ａによりセル内に導かれ
る。The neural model device according to the present embodiment further includes:
A light source 14 and a light guide 14a are provided so that the lipid-impregnated membrane 13 can be irradiated with light. Light emitted from the light source 14 is guided into the cell by the light guide 14a.
【００１４】セル１１の素材は、脂質含浸膜１３との関
係で有機溶媒耐性のある材質が好ましく、本実施例では
フッ素樹脂製セルを使用する。セル１１中のイオン性水
溶液１２はサーキュレーター１５により温度制御され
る。Ｘ槽及びＹ槽には、それぞれ塩橋１６ａ、１ｍｏｌ
／ｌのＫＣｌ水溶液１６ｂ及び銀／塩化銀電極１６ｃか
らなる電極１６が設置してある。このようにして、本実
施例においては、フッ素樹脂製のセルを脂質含浸膜１３
で仕切り形成して、各セルに電極を設置して構成してい
る。The material of the cell 11 is preferably a material having an organic solvent resistance in relation to the lipid-impregnated membrane 13. In this embodiment, a fluororesin cell is used. The temperature of the ionic aqueous solution 12 in the cell 11 is controlled by a circulator 15. In the X tank and the Y tank, the salt bridge 16a, 1 mol, respectively
The electrode 16 is composed of an aqueous KCl solution 16b / l and a silver / silver chloride electrode 16c. Thus, in the present embodiment, the cell made of the fluororesin is replaced with the lipid-impregnated membrane 13.
, And electrodes are provided in each cell.
【００１５】電極１６から得られた電気振動信号は、バ
ッチクランプ用アンプ１７ａ、オシロスコープ１７ｂ、
フィルタ１７ｃ、テープレコーダ１７ｄ、チャートレコ
ーダ１７ｅ、コンピュータ１７ｆからなる情報処理部１
７に送られる。The electric vibration signal obtained from the electrode 16 is supplied to a batch clamp amplifier 17a, an oscilloscope 17b,
Information processing unit 1 including filter 17c, tape recorder 17d, chart recorder 17e, and computer 17f
7
【００１６】なお、以上の脂質含浸膜測定系は、シール
ドボックス１８及び除振台１９を設置することで、防音
及び防振によるノイズ対策が施されている。また、脂質
含浸膜測定系に熱伝導が生じないように、光源１４は、
ヒートアブソープションフィルタ１４ｂを介してシール
ドボックス１８の外に配置してある。従って、ヒートア
ブソープションフィルタ１４ｂにより、光源１４からの
熱伝導が防止されるようになっている。The above-mentioned lipid-impregnated membrane measuring system is provided with a shield box 18 and an anti-vibration table 19, thereby taking measures against noise by noise and vibration. The light source 14 is provided so that heat conduction does not occur in the lipid-impregnated membrane measurement system.
It is arranged outside the shield box 18 via the heat absorption filter 14b. Therefore, heat conduction from the light source 14 is prevented by the heat absorption filter 14b.
【００１７】また、本実施例においては、光源１４はＸ
槽側に配置されＸ槽側から光照射が行われているが、脂
質含浸膜１３はある程度透明であるため光源１４はＹ槽
側に配置してもよい。In this embodiment, the light source 14 is X
Although the light irradiation is performed from the X tank side arranged on the tank side, the light source 14 may be arranged on the Y tank side because the lipid-impregnated membrane 13 is transparent to some extent.
【００１８】本実施例においては、脂質含浸膜１３に
は、イオンポンプ及びイオンチャネルが埋設されてい
る。以下、これについて詳細に説明する。In this embodiment, an ion pump and an ion channel are embedded in the lipid-impregnated membrane 13. Hereinafter, this will be described in detail.
【００１９】［脂質含浸膜の作製方法］脂質含浸膜とは
脂質が含浸されている膜のことを言い、脂質含浸性膜
（脂質を含浸することができる性質を有する膜）に脂質
を含浸させて作製する。ここで、脂質が含浸させられる
脂質含浸性膜には、一般的には多孔膜が使用される。本
実施例では、直径１０ｍｍφ程度（若しくはそれ以上）
の大きさの多孔膜（孔径０．１μｍφ、膜厚０．１５ｍ
ｍ程度）を、アゾレクチン（脂質）の２００ｍｇ／ｍｌ
のノルマルデカン溶液に数秒間浸漬して作製した。この
ような脂質含浸膜は、膜の作製が容易で強度が大きいと
いう利点がある。なお、多孔膜としては、セルロース
膜、ニトロセルロース膜、トリアセチルセルロース等の
セルロース混合エステルまたはポリテトラフルオロエチ
レン、ポリカーボネイト等を使用する。[Preparation Method of Lipid-Impregnated Membrane] A lipid-impregnated membrane is a membrane impregnated with lipid, and is obtained by impregnating a lipid into a lipid-impregnated membrane (a membrane having a property capable of impregnating lipid). To make. Here, a porous membrane is generally used for the lipid-impregnated membrane impregnated with lipid. In this embodiment, the diameter is about 10 mmφ (or more).
Size porous membrane (pore diameter 0.1 μmφ, film thickness 0.15 m
m) with 200 mg / ml of azolectin (lipid)
For several seconds in a normal decane solution. Such a lipid-impregnated membrane has the advantage that the membrane is easy to produce and has high strength. As the porous film, a cellulose mixed ester such as a cellulose film, a nitrocellulose film, and triacetyl cellulose, or polytetrafluoroethylene, polycarbonate, or the like is used.
【００２０】［神経モデル素子の作製］ ［脂質含浸膜を用いた神経モデル素子の作製方法］図２
は、本実施例に係る神経モデル素子の作製方法を示す工
程図である。[Preparation of Neural Model Element] [Method of Preparing Nerve Model Element Using Lipid Impregnated Membrane] FIG.
FIG. 4 is a process chart showing a method for manufacturing a nerve model element according to the present embodiment.
【００２１】本実施例に係る神経モデル素子は、合わせ
面に穴２１が開いているフッ素樹脂製の２つのセル１１
ａ及び１１ｂを（図２（Ａ））、上記脂質含浸膜１３を
挟み合わせて作製した（図２（Ｂ））。このように、穴
２１が開いている合わせ面に脂質含浸膜１３を挟み合わ
されることで、２つの槽が脂質含浸膜で仕切られた構造
が形成される（図２（Ｃ））。穴２１は、そのままホー
ルＨ（図１）を構成する。実施例において、合わせ面に
開いている穴２１は７〜８ｍｍφであり、フッ素樹脂製
の２つのセル１１ａ及び１１ｂの容積はそれぞれ１．５
ｃｃである。The nerve model element according to this embodiment has two cells 11 made of fluororesin and having a hole 21 in the mating surface.
a and 11b were produced by sandwiching the lipid-impregnated membrane 13 (FIG. 2A) (FIG. 2B). In this manner, by sandwiching the lipid-impregnated membrane 13 on the mating surface where the holes 21 are opened, a structure in which the two tanks are separated by the lipid-impregnated membrane is formed (FIG. 2C). The hole 21 forms the hole H (FIG. 1) as it is. In the embodiment, the hole 21 opened in the mating surface has a diameter of 7 to 8 mm, and the two fluorocarbon resin cells 11a and 11b each have a capacity of 1.5 mm.
cc.
【００２２】［イオンポンプ埋設方法］イオンポンプを
埋設するために、上記セルの一方に、イオンポンプを含
む水溶液を注入し、イオンポンプを脂質含浸膜に吸着さ
せるようにした。本実施例ではイオンポンプとして紫膜
を使用した。[Ion Pump Embedding Method] In order to embed the ion pump, an aqueous solution containing the ion pump was injected into one of the cells, and the ion pump was adsorbed on the lipid-impregnated membrane. In this embodiment, a purple membrane was used as an ion pump.
【００２３】紫膜の埋設は、 L.A.Drachev, et al., An
alytical Biochemistry 96 (1979)250-262 及び M.C.Bl
ock, et al., FEBS Letters 76 (1) (1977) 45-50に示
される方法と同様の方法で行った。The embedding of the purple membrane is described in LADrachev, et al., An
alytical Biochemistry 96 (1979) 250-262 and MCBl
ock, et al., FEBS Letters 76 (1) (1977) 45-50.
【００２４】すなわち、本実施例において、イオンポン
プを含む水溶液は、タンパク質の質量換算で１．５ｍｇ
の紫膜を水に溶かして１．０ｍｌにしたものを使用し
た。この水溶液４０μｌを注入し、１時間程度撹拌する
ことで、イオンポンプ（紫膜）が脂質含浸膜に埋設され
る。That is, in this embodiment, the aqueous solution containing the ion pump contained 1.5 mg of protein in terms of mass.
Was dissolved in water to make 1.0 ml. By injecting 40 μl of this aqueous solution and stirring for about 1 hour, the ion pump (purple membrane) is embedded in the lipid-impregnated membrane.
【００２５】但し、ここでイオンポンプの埋設方法は、
紫膜の膜片そのものあるいは可溶化したバクテリオロド
プシンを添加してもよく、しかもそれらをリポソームに
再構成したものを使用してもよい。However, the method of burying the ion pump here is as follows.
A purple membrane piece itself or solubilized bacteriorhodopsin may be added, and those reconstituted into liposomes may be used.
【００２６】なお、脂質含浸膜はある程度透明なため、
光源１４を逆側に配置しても同様の振動が得られるが、
光が膜に吸収される分だけ効率は落ちるため、光源１４
は、イオンポンプが埋設された側に配置されることが好
ましい。Since the lipid-impregnated membrane is transparent to some extent,
A similar vibration can be obtained by disposing the light source 14 on the opposite side,
The efficiency is reduced by the amount of light absorbed by the film.
Is preferably arranged on the side where the ion pump is embedded.
【００２７】［イオンチャンネルの埋設方法］イオンチ
ャンネルの埋設は、予め水が入っている２つのセル１１
ａ及び１１ｂに、アラメシチン（イオンチャンネル）１
ｍｇ／ｌのエタノール溶液を２０μｌ添加することで行
った。これにより、アラメシチンが脂質含浸膜１３に再
構成される。[Embedding Method of Ion Channel] The embedding of the ion channel is performed by using two cells 11 containing water in advance.
Alamecithin (ion channel) 1 in a and 11b
This was performed by adding 20 μl of a mg / l ethanol solution. Thereby, alamesitin is reconstituted in the lipid-impregnated membrane 13.
【００２８】［動作］本実施例の神経モデル素子におい
ては、イオンチャネル及びイオンポンプが埋設された脂
質含浸膜１３に光を照射すると、イオンチャネルが駆動
して脂質含浸膜１３に膜電位を生じさせる。そして、生
じた膜電位が所定の大きさになると、イオンチャネルが
開いて膜電位が解消される。膜電位が解消されると、イ
オンチャネルが閉じる。すると、イオンポンプの作動に
より再び膜電位が生じる。以上の行程を繰り返すこと
で、膜電位差の一定周期の増減現象を得ることができ、
この変化を電極１６により捉え、これが電極により電気
振動信号として得られる。[Operation] In the nerve model element of this embodiment, when light is applied to the lipid-impregnated membrane 13 in which the ion channel and the ion pump are embedded, the ion channel is driven to generate a membrane potential in the lipid-impregnated membrane 13. Let it. Then, when the generated membrane potential reaches a predetermined magnitude, the ion channel is opened and the membrane potential is eliminated. When the membrane potential is released, the ion channel closes. Then, the membrane potential is generated again by the operation of the ion pump. By repeating the above steps, it is possible to obtain a phenomenon of increasing and decreasing the membrane potential difference in a constant cycle,
This change is captured by the electrode 16, and this is obtained as an electric vibration signal by the electrode.
【００２９】［神経モデル素子の発振測定］図３は、ア
ラメシチンのＩ−Ｖ特性（アラメシチン添加側が正）を
表したグラフである（ G.Andrew, et al., J.Menbrane
Biol. 129 (1992) 109-136）。[Oscillation Measurement of Neural Model Element] FIG. 3 is a graph showing the IV characteristics of alamesitin (alamecithin added side is positive) (G. Andrew, et al., J. Menbrane).
Biol. 129 (1992) 109-136).
【００３０】また、図４は、本実施例に係る神経モデル
素子により得られる電気振動信号を示す図である。図４
において、αはアラメシチン（イオンチャネル）なし
（即ち紫膜（イオンポンプのみ））の場合の光応答を、
βは１１ｂ側のベース電圧を４０ｍＶまで上昇させたと
きの光応答を、γは１１ｂ側にアラメシチンを添加した
際の光応答をそれぞれ示している。FIG. 4 is a diagram showing an electric vibration signal obtained by the nerve model element according to the present embodiment. FIG.
In α, the light response in the absence of alamesitin (ion channel) (ie, purple membrane (only ion pump))
β indicates the optical response when the base voltage on the 11b side is increased to 40 mV, and γ indicates the optical response when alamesitin is added to the 11b side.
【００３１】図３よりアラメシチンが存在すると、６０
ｍＶ付近で急激に電導度が上昇することがわかる。これ
に鑑みて、紫膜（イオンポンプ）の働きにより生じる膜
電位がこの電位に達するようにベース電圧を上昇させる
と、図４のγに示されるような振動が得られた。このよ
うにして得られる膜電位差の増減現象からなる電気振動
信号は、生体膜における振動現象とが極めて類似してい
る。As shown in FIG.
It can be seen that the conductivity sharply increases near mV. In view of this, when the base voltage was increased so that the membrane potential generated by the action of the purple membrane (ion pump) reached this potential, oscillation as shown by γ in FIG. 4 was obtained. The electric vibration signal obtained from the phenomenon of increasing and decreasing the membrane potential difference obtained in this manner is very similar to the vibration phenomenon in the biological membrane.
【００３２】以上のようにして、本実施例の神経モデル
素子は、外部刺激（光照射あるいは基質の添加等）によ
りイオンポンプのイオン輸送能力を制御することが可能
なため、外部刺激に対応した任意の振動モードを有する
電気振動信号を得ることができる。As described above, the nerve model element of the present embodiment can control the ion transport ability of the ion pump by external stimulus (light irradiation or addition of substrate, etc.). An electric vibration signal having an arbitrary vibration mode can be obtained.
【００３３】なお、本実施例においては、イオンチャン
ネルとしてアラメシチン、イオンポンプとして紫膜を用
いているが、イオンポンプ及びイオンチャンネルはこれ
らに限られることなく、また脂質含浸膜についても本実
施例に用いた材料に限られることなく、他の物質を用い
ても所定の電気振動信号を得ることができる。In this embodiment, alamecithin is used as the ion channel and purple membrane is used as the ion pump. However, the ion pump and the ion channel are not limited to these, and the lipid-impregnated membrane is also used in this embodiment. A predetermined electric vibration signal can be obtained even if another substance is used without being limited to the material used.
【００３４】[0034]
【発明の効果】以上説明したように、本発明によれば、
外部刺激により膜電位差を増大させるイオンポンプとこ
の膜電位差により開き膜電位差を減少させるイオンチャ
ネルを組み合わせて脂質薄膜に埋設することにより、膜
電位差の一定周期の増減現象を得ることができ、外部刺
激に対応した任意の振動モードを有する電気振動信号を
得ることができる。これは、生体情報処理の根幹となる
振動要素でありバイオコンピュータの礎となり得るもの
である。As described above, according to the present invention,
By embedding in a lipid thin film a combination of an ion pump that increases the membrane potential difference by an external stimulus and an ion channel that opens the membrane potential difference and reduces the membrane potential difference, it is possible to obtain a constant period increase and decrease phenomenon of the membrane potential difference An electric vibration signal having an arbitrary vibration mode corresponding to the above can be obtained. This is a vibration element that is the basis of biological information processing and can be the basis of a biocomputer.
【図１】本発明の好適な実施例に係る神経モデル素子の
膜電位測定系を示す模式図である。FIG. 1 is a schematic diagram showing a membrane potential measuring system of a nerve model device according to a preferred embodiment of the present invention.
【図２】脂質含浸膜を使用した本発明の実施例に係る神
経モデル素子の作製方法を示す工程図である。FIG. 2 is a process chart showing a method for producing a nerve model device according to an embodiment of the present invention using a lipid-impregnated membrane.
【図３】アラメシチンの電圧電流曲線（アラメシチン添
加側が正）を示すグラフである。FIG. 3 is a graph showing a voltage-current curve of alamesitin (alamecithin-added side is positive).
【図４】本発明の実施例に係る神経モデル素子により得
られる電気振動信号を示す図である。ここで、αはアラ
メシチン（イオンチャネル）なし（即ち紫膜（イオンポ
ンプのみ））の場合の光応答を、βはベース電圧を４０
ｍＶまで上昇させたときの光応答を、γはアラメシチン
添加した際の光応答をそれぞれ示している。FIG. 4 is a diagram showing an electric vibration signal obtained by the nerve model element according to the embodiment of the present invention. Here, α is the photoresponse without alamesitin (ion channel) (ie, purple membrane (only ion pump)), and β is the base voltage of 40.
The light response when the voltage was increased to mV, and γ indicates the light response when alamesitin was added.
１１ セル １１ａ，１１ｂ セル １２ イオン性水溶液 １３ 脂質含浸膜 １４ 外部刺激（光源） １４ａ ライトガイド １５ サーキュレーター １６ 電極 １６ａ 塩橋 １６ｂ 水溶液 １６ｃ 銀／塩化銀電極 １７ 情報処理部 １７ａ バッチクランプ用アンプ １７ｂ オシロスコープ １７ｃ フィルタ １７ｄ テープレコーダ １７ｅ チャートレコーダ １７ｆ コンピュータ １８ シールドボックス １９ 除振台 ２１ 穴 Reference Signs List 11 cell 11a, 11b cell 12 ionic aqueous solution 13 lipid-impregnated membrane 14 external stimulus (light source) 14a light guide 15 circulator 16 electrode 16a salt bridge 16b aqueous solution 16c silver / silver chloride electrode 17 information processing unit 17a batch clamp amplifier 17b oscilloscope 17c Filter 17d Tape recorder 17e Chart recorder 17f Computer 18 Shield box 19 Anti-vibration table 21 hole
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 平４−52986（ＪＰ，Ａ) 特開 平４−52527（ＪＰ，Ａ) 特開 平３−163886（ＪＰ，Ａ) (58)調査した分野(Int.Cl.7，ＤＢ名) G06G 7/60 B01J 13/02 C09K 3/00 G01J 1/00 ────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-4-52986 (JP, A) JP-A-4-52527 (JP, A) JP-A-3-163886 (JP, A) (58) Field (Int.Cl. 7 , DB name) G06G 7/60 B01J 13/02 C09K 3/00 G01J 1/00
Claims (2)
であって、 容器に貯留されたイオン性水溶液と、 前記イオン性水溶液を仕切る脂質含浸膜であって、外部
刺激により作動し前記イオン性水溶液中のイオンを能動
輸送するイオンポンプ及び該脂質含浸膜の両側の膜電位
差がある閾値に達することで開くイオンチャネルが埋設
されている脂質含浸膜と、 前記脂質含浸膜に外部刺激を付与する手段と、 前記脂質含浸膜の膜電位を電気信号として伝達する電極
と、 を含むことを特徴とする神経モデル素子。1. A nerve model element for generating an electric vibration signal, comprising: an ionic aqueous solution stored in a container; and a lipid-impregnated membrane for partitioning the ionic aqueous solution, wherein the ionic aqueous solution is activated by an external stimulus. An ion pump that actively transports ions therein, a lipid-impregnated membrane in which an ion channel that opens when the membrane potential difference on both sides of the lipid-impregnated membrane reaches a certain threshold, and a means for applying an external stimulus to the lipid-impregnated membrane And an electrode for transmitting the membrane potential of the lipid-impregnated membrane as an electric signal.
ンを用いることを特徴とする請求項１記載の神経モデル
素子。2. The nerve model device according to claim 1, wherein bacteriorhodopsin is used for the ion pump.
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|---|---|---|---|
| JP05080667A JP3128386B2 (en) | 1993-04-07 | 1993-04-07 | Neural model element |
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| JP05080667A JP3128386B2 (en) | 1993-04-07 | 1993-04-07 | Neural model element |
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| JP3128386B2 true JP3128386B2 (en) | 2001-01-29 |
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| US9101759B2 (en) | 2008-07-08 | 2015-08-11 | The Board Of Trustees Of The Leland Stanford Junior University | Materials and approaches for optical stimulation of the peripheral nervous system |
| NZ602416A (en) | 2008-11-14 | 2014-08-29 | Univ Leland Stanford Junior | Optically-based stimulation of target cells and modifications thereto |
| SG10201505162QA (en) | 2010-03-17 | 2015-08-28 | Univ Leland Stanford Junior | Light-sensitive ion-passing molecules |
| CN103384469B (en) | 2010-11-05 | 2016-06-15 | 斯坦福大学托管董事会 | Light-controlled CNS dysfunction |
| CN103313752B (en) | 2010-11-05 | 2016-10-19 | 斯坦福大学托管董事会 | Upconversion of Light for Optogenetic Approaches |
| EP2635108B1 (en) | 2010-11-05 | 2019-01-23 | The Board of Trustees of the Leland Stanford Junior University | Light-activated chimeric opsins and methods of using the same |
| US8696722B2 (en) | 2010-11-22 | 2014-04-15 | The Board Of Trustees Of The Leland Stanford Junior University | Optogenetic magnetic resonance imaging |
| CN107936097A (en) | 2011-12-16 | 2018-04-20 | 斯坦福大学托管董事会 | Opsin polypeptide and its application method |
| US9636380B2 (en) | 2013-03-15 | 2017-05-02 | The Board Of Trustees Of The Leland Stanford Junior University | Optogenetic control of inputs to the ventral tegmental area |
| US10220092B2 (en) | 2013-04-29 | 2019-03-05 | The Board Of Trustees Of The Leland Stanford Junior University | Devices, systems and methods for optogenetic modulation of action potentials in target cells |
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