NG108-15細胞のATPにより誘発される非選択性陽イオン電流 Mechanism of Ca^<2+> influx by extracellular ATP in NG108-15 cells

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ATP at 100 μM induced a trasient [Ca<SUP>2+</SUP>]<SUB>i</SUB> increase, while at 1 mM it induced the transient increase followed by a sustained [Ca<SUP>2+</SUP>]<SUB>i</SUB> increase in NG108-15 cells. We examined the mechanism of this sustained [Ca<SUP>2+</SUP>] increase using the fura-2 fluorescent method and the whole-cell patch clamp technique. Pretreatment of the cells with U73122 (PLC inhibtor) completely inhibited the trasient [Ca<SUP>2+</SUP>]<SUB>i</SUB> increase but not the sustained [Ca<SUP>2+</SUP>]<SUB>i</SUB> increase by ATP. The sustained [Ca<SUP>2+</SUP>]<SUB>i</SUB> increase was not observed in the absence of extracellular Ca<SUP>2+</SUP>, suggesting that this component was due to Ca<SUP>2+</SUP> influx. Under the whol-cell patch clamp, 1 mM ATP induced a membrane current with the reversal potential at 12.5±0.8 mV in Tyrode solution with the Cs<SUP>+</SUP> aspartate pipete solution. The ATP-induced current increased in a concentration dependent manner with EC<SUB>50</SUB> value of approximately 0.75 mM ATP. When external Na<SUP>+</SUP> was replaced by Li<SUP>+</SUP>, K<SUP>+</SUP>, Rb<SUP>+</SUP>, Cs<SUP>+</SUP> or NMG<SUP>+</SUP>, ATP induced the current with a slight shift in the reversal potentials, suggesting that ATP activated a nonselective cation current. From the reversal potentials, the permeability ratio was calculated to be Na<SUP>+</SUP> (1) > Li<SUP>+</SUP> (0.93) > K<SUP>+</SUP> (0.89) > Rb<SUP>+</SUP> (0.56) > Cs<SUP>+</SUP> (0.47) > NMG<SUP>+</SUP> (0.12). Upon total replacement of external cation with Ca<SUP>2+</SUP>, ATP could induce the current, inicating that Ca<SUP>2+</SUP> was permeable through the current. The permeability ratio of Ca<SUP>2+</SUP> : Na<SUP>+</SUP> was 1 : 0.6. ATP analogues which induced the current were 2MeSATP, BzATP, ATPγs and ADPβs. UTP had only a small effect and adenosine did not induce any current. α, β MetATP, β, γMetATP and ADP induced a different type of current. In fura-2 fluorescent method, ATPγs increased [Ca<SUP>2+</SUP>]<SUB>i</SUB> sustaindly but α, β MetATP and β, γ MetATP did not do so. These results indicated that ATP induced a nonselective cation current via P<SUB>2Z</SUB> receptor subtype. ATP-induced current was larger at lower [Mg<SUP>2+</SUP>]<SUB>o</SUB>, indicating that ATP<SUP>4-</SUP> was an effective agonist form of ATP. Calculated EC<SUB>50</SUB> value was 21.5 μM ATP<SUP>4-</SUP>. We conclude that a high concentration of ATP stimulates P<SUB>2Z</SUB> receptor which is coupled to a class of Ca<SUP>2+</SUP>-permeable nonselective cation channels through which Ca<SUP>2+</SUP> influx occurs in NG 10815 cells.

収録刊行物

  • 日本薬理学雑誌

    日本薬理学雑誌 106, 138-142, 1995-09-01

    公益社団法人 日本薬理学会

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