Potentiating Actions of Lanthanum on ACh-Induced Cation Current in Guinea-Pig Ileal Smooth Muscle Cells
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概要
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Potentiating actions of external lanthanum(La^<3+>)on muscarinic receptor-activated nonselective cation current(I_<cat>)were investigated in myocytes dissociated from the longitudinal muscle layer of guinea-pig ileum, with a whole-cell variant of the patch clamp technique. I_<cat> was dissected from other membrane currents by loading Cs-aspartate into the cell. Application of submilimolar concentrations of La^<3+> following 300 μM ACh into the bath caused a dose-dependent increase in the amplitude of I_<cat>. The apparent Kd value for this increase was 190 μM, with a cooperativity factor of 1.7. La^<3+>-induced increase in I_<cat> amplitude was not associated with either changes in the reversal potential of I_<cat> or altered sensitivity of muscarinic receptor to ACh, and paralleled by the conductance increase of I_<cat>, the maximum of which(G_<max>)occurred at about 1 mM La^<3+>. Voltage-jump experiments revealed that the rate of current relaxation at hyperpolarizing potentials was greatly reduced in the presence of La^<3+>, and correspondingly the steady state activation curve shifted toward more negative potentials. Divalent cations such as Cd^<2+> or Ni^<2+>, which have been known to block I_<cat>, antagonized the augmentative effect of La^<3+> on I_<cat> in a competitive fashion, suggesting that the site of their actions might be similar. Furthermore, single I_<cat> activities induced by internal perfusion of GTPγS(100 μM)was also greatly enhanced by external addition of 1 mM La^<3+>. Under current clamp conditions, 1 mM L^<3+> blocked spontaneous Ca^<2+> spike activities, but was almost without effect on the membrane depolarization induced by ACh. In contrast, milimolar concentrations of Cd^<2+> and Ni^<2+> abolished both Ca^<2+> spike activities and ACh-induced depolarization. Potential importance of La^<3+> as a tool to investigate the external Ca^<2+>-dependence of I_<cat> has been discussed.
- 日本平滑筋学会の論文
著者
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Ito Y
Department Of Pharmacology Graduate School Of Medical Sciences Kyushu University
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MORITA Hiromitsu
Department of Pharmacology, College of Medicine, University of Vermont
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Inoue Ryuji
Department Of Physiology School Of Medicine Fukuoka University
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Inoue Ryuji
Department Of Pharmacology Faculty Of Medicine Kyushu University
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Ito Yushi
Department Of Neonatology National Center For Child Health And Development
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YANAGIDA Hiroe
Department of Pharmacology, Faculty of Medicine, Kyushu University
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Yanagida Hiroe
Department Of Pharmacology Faculty Of Medicine Kyushu University
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Inoue Ryuji
Special Patient Oral Care Unit Kyushu University Hospital
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Morita Hiromitsu
Special Patient Oral Care Unit Kyushu University Hospital
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Ito Yushi
Department of Health Science, Kumamoto Health Science University
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