기니피그 위 평활근의 자발적 수축과 전기적 활동에 대한 Ca²⁺ 및 Ca²⁺-길항제 영향

Effect of Ca²⁺ and Ca²⁺-antagonists on the Spontaneous Contractions and Electrical Activities of Guinea-pig Stomach

The effects of external Ca²⁺ and Ca²⁺-antagonists on the spontaneous contractions and electrical activities were investigated in guinea-pig stomach in order to clarify the mechanism for the generation of slow waves. Electrical responses of circular smooth muscle cells were recorded using glass capillary microelectrodes filled with 3 M KCl. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% O² and kept at 35℃. The results obtained were as follows: 1) The amplitude of spontaneous contractions was maximal at around 2-4 mM Ca²⁺, whereas their frequency was inversely related with external Ca²⁺ within the range of 0.5 to 16 mM Ca²⁺. 2) Verapamil suppressed the amplitude of spontaneous contraction in a dose-dependent manner, while the frequency of spontaneous contractions was almost not changed over the whole concentration of verapamil (0.01 ~ 5 mg/l). 3) Manganese increased both the amplitude and the frequency of spontaneous contractions dose-dependently in low Mn²⁺ (below 0.05 mM Mn²⁺), while their amplitude and frequency were decreased in high Mn²⁺ (above 0.1 mM Mn²⁺). 4) The ampltude and maximum rate of rise of slow waves were incrased in high Ca²⁺ solution. In Ca²⁺-free solution, the spontaneous contractions recorded simultaneously with slow waves ceased and tonic contraction (Ca²⁺-free contracture) was developed in parallel with membrane depolarization and the disappearance of slow waves. 5) Verapamil (1 mg/1) decreased the amplitude and maximum rate of rise of slow waves and it depolarized the membrane by about 6 mV, whereas the frequency of slow waves was not affected by verapamil. 6) Manganese showed different characteristic effects between low and high Mn²⁺ on the slow waves: In low Mn²⁺ (0.05 mM Mn²⁺), the initial rapid increases and the subsequent gradual decreases in three parameters of slow waves (amplitude, rate of rise, and frequency of slow waves) till a new steady state were observed. However, in high Mn²⁺ (0.5 mM Mn²⁺) slow waves disappeared and membrane was depolarized. From the above results, the following conclusions could be made: 1) Ca²⁺ is necessary for a generation of the slow waves, even though it is small amount. 2) Verapamil suppresses the spontaneous contractions of gastric antral strip by the decreases in amplitude and maximum rate of rise of slow waves, while this drug does not block the Ca²⁺-channel involved in the generation of slow waves. 3) Manganese has dual actions on the Ca²⁺-channels; the Ca²⁺-channel involved in the generation of slow waves (or Na-Ca exchange system) or the channel for the generation of spike potentials are stimulated by a low concentration of Mn²⁺, while both the Ca²⁺. Channels are blocked by high concentration of Mn²⁺.