Effects of Lemakalim, a Potassium Channel Opener, on the Contractility and Electrical Activity of the Antral Circular Muscle in Guinea-Pig Stomach

• 영문명: Effects of Lemakalim, a Potassium Channel Opener, on the Contractility and Electrical Activity of the Antral Circular Muscle in Guinea-Pig Stomach
• 발행기관: 대한생리학회
• 저자명: Kim, Sung-Joon Jun, Jae-Yeoul Choi, Youn-Baik Kim, Ki-Whan Kim, Woo-Gyeum
• 간행물 정보: 『대한생리학회지』제28권 제1호, 37~50쪽, 전체 14쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 1994.06.30

영문 초록

Synthetic potassium channel openers (KCOs) are agents capable of opening K-channels in excitable cells. These agents are known to have their maximal potency in the smooth muscle tissue, especially in the vascular smooth muscle. Much attention has been focused on the type of K-channel that is responsible for mediating the effects of KCOs. As the KCO-induced changes are antagonized by glibenclamide, an K_ATP (ATP-sensitive K-channel) blocker in the pancreatic β-cell, K_ATP was suggested to be the channel responsible. However, there also are many results in favor of other types of K-channel $(maxi-K, small conductance K_Ca SK_ATP) mediating the effects of KCOs. Effects of lemakalim, (-)enantiomer of cromakalim (BRL 34915), on the spontaneous contractions and slow waves, were investigated in the antral circular muscle of the guinea-pig stomach. Membrane currents and the effects on membrane currents and single channel activities were also measured in single smooth muscle cells and excised membrane patches by using the patch clamp method. Lemakalim induced hyperpolarization and inhibited spontaneous contractions in a dose-dependent manner. These effects were blocked by glibenclamide and low concentrations of tetraethyl ammonium (< mM). Glibenclamide blocked the effect of lemakalim on the membrane potential and slow waves. The mechanoinhibitory effect of lemakalim was blocked by pretreatment with glibenclamide. In a whole ceIl patch clamp condition, lemakalim largely increased outward K currents. These outward K currents were blocked by TEA, glibenclamide and a high concentration of intracelIular EGTA (10 mM). Volatage-gated Ca currents were not affected by lemakalim. In inside-out patch clamp experiments, lemakalim increased the opening frequency of the large conductance Ca²⁺-activated K channels (BK_Ca, Maxi-K). From these results, it is suggested that lemakalim induces hyperpolarization by opening K-channels which are sensitive to internal Ca and such a hyperpolarization leads to the inhibition of the spontaneous contraction.

키워드

K channel opener Gastric smoth muscle Slow wave Membrane current