子宮平滑筋の収縮および電気的活動性の妊娠による変化と生理活性物質の効果に関する電気生理学的研究(1子宮収縮機構とその制御)

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Uterine contraction consists of 3main factors, i. e., 1) amplitude, 2) duration, and 3) frequency. It is generally accepted that uterine contraction and relaxation mainly depend on the electrical activity of cell membrane. From this point of view, it seems to be important to analyze the electrical activity of myometrim into the level of activity of ionic channels. The aim of this study is to elucidate what kind of ion channels are involved in the electrical activity of myometrium, whether or not the change of ionic channels happens during pregnancy, and to clarify how uterotonic and tocolytic agents act on ionic channels of art and human myometrium by the electrophysiological methods. Isotonic contraction recording, intracellular microelectrode methods and patch-clamp method were used. The resting membrane potentials of both species were around-50 mV and in rats, it gradually depolarized towards the term. 2 types of action potentials, namely a spike type and aplateau type could be recognized both in rat and human myometrium. In rat calcium ion was important to generate action potential. On the other hand, both sodium and calcium ions were important to generate action potentials in human myometrium. Rat myometrium possessed two kinds of inward currents, fast sodium and slow calcium channel currents and the former was inhibited by tetrodotoxin. The number of fast sodium channels increased almost linearly during gestation. This increase occurred because of an increase in the fraction of cells that possessed fast sodium channels. The calcium channel current density was also higher during the latter half of gestation. Two kinds of voltage-dependent potassium channels and also calcium-dependent potassium channels existed in rat myometrium. Furthermore pregnant rat circular smooth muscle possesses hyperpolarization-activated in ward current (Ih) , but longitudinal smooth muscle not. Ih was inhibited by extracellular cesium ion as that of cardiac SA node cells and was supposed to act as the pacemaking current. In freshly dispersed human myometrial cells, we could not find sodium current, but could record two kinds of calcium currents, namely T and L type. These results suggested that the distribution of ionic channels differs between two species. In rat myometrium oxytocin could not affect either calcium, sodium or potassium channel currents, but induced a non-selective cation channel currents. It is speculated that oxytocin increases intracellular calcium concentration ([Ca^<2+>]_i) by the mechanism described below. For the first, oxytocin may depolarize the membrane by induction of non-selective cation channel currents, and then voltage-dependent calcium channels may be secondarily activated by this depolarization, and consequently[Ca^<2+>]_i increases. Oxytocin also acts on intracellular calcium store to release calcium, but the contribution of this released calcium may be small. The number of oxytocin receptors in myometrium and the maternal plasma oxytocin concentration in rat increased near the onset of parturition both in term and preterm labor. Furthermore an oxytocin antagonist L366, 509 delayed the initiation of labor in rats with term and preterm labor. There results suggested that oxytocin may have the important role to initiate the labor. In rats, isoproterenol (β-agonist) did not affect either calcium or sodium currents, whereas magnesium and nifedipine depressed calcium currents in dose-dependent manner. 17β-estradiol also inhibited both calcium and potassium channels in pregnant rat. It can be conclued that many types of ionic channels are involved in regulation of mechanical and electrical activity of myometrium even thought there is a small difference between the species and that the change of channel density took place during the pregnancy to make the myometrium more excitable near term. Many uterotonic and tocolytic agents modulate uterine contraction by acting on ionic channels of myometrium.
社団法人日本産科婦人科学会の論文
2000-08-01

子宮平滑筋の収縮および電気的活動性の妊娠による変化と生理活性物質の効果に関する電気生理学的研究(1子宮収縮機構とその制御)

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