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Myometrial relaxation of mice via expression of two pore domain acid sensitive K + (TASK-2) channels

View Article: PubMed Central - PubMed

ABSTRACT

Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing K+ channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward K+ current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing K+ channels (TASK-2). NIOK in the presence of K+ channel blockers was inhibited further by TASK inhibitors such as quinidine, bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine and increased immunohistochemical expression of TASK-2. Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in the longitudinal myometrium of mouse. Activation of TASK-2 channels seems to play an essential role for relaxing uterus during pregnancy and it might be one of the alternatives for preventing preterm delivery.

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Effect of quinidine on the isometric contraction of uterine longitudinal muscle in mice.(A) Oxytocin (OXT) produced initial and tonic contractions; however, tonic contractions were not sustained in non-pregnant myometrium (NP, non-pregnant; TP, term-pregnant). (B) Quinidine (10, 20, and 30 µM) produced concentration-dependent phasic contractions. Tonic contractions were also produced at high concentrations of quinidine in pregnant myometrium. (C) Quinidine was applied to myometrium in the presence of TEA (10 mM). TEA (10 mM) produced strong phasic contractions in non-pregnant myometrium (1.2±0.15 g) but not in pregnant myometrium. Quinidine (10~30 µM), even in the presence of TEA, increased contraction frequency in non-pregnant myometrium and produced stronger contractions in pregnant myometrium.
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Figure 1: Effect of quinidine on the isometric contraction of uterine longitudinal muscle in mice.(A) Oxytocin (OXT) produced initial and tonic contractions; however, tonic contractions were not sustained in non-pregnant myometrium (NP, non-pregnant; TP, term-pregnant). (B) Quinidine (10, 20, and 30 µM) produced concentration-dependent phasic contractions. Tonic contractions were also produced at high concentrations of quinidine in pregnant myometrium. (C) Quinidine was applied to myometrium in the presence of TEA (10 mM). TEA (10 mM) produced strong phasic contractions in non-pregnant myometrium (1.2±0.15 g) but not in pregnant myometrium. Quinidine (10~30 µM), even in the presence of TEA, increased contraction frequency in non-pregnant myometrium and produced stronger contractions in pregnant myometrium.

Mentions: OXT treatment produced tonic contractions superimposed with phasic contractions. Initial peak contractions induced by OXT were 1.5±0.18 g (non-pregnant, n=48, 38) and 2.1±0.20 g (pregnant, n=32, 38), respectively. Tonic contractions were 0.5±0.07 g (non-pregnant, n=48, 46) and 2.0±0.20 g (pregnant, n=32, 38) (Fig. 1A). Tonic contractions induced by OXT were significantly different in non-pregnant and pregnant myometrial tissues.


Myometrial relaxation of mice via expression of two pore domain acid sensitive K + (TASK-2) channels
Effect of quinidine on the isometric contraction of uterine longitudinal muscle in mice.(A) Oxytocin (OXT) produced initial and tonic contractions; however, tonic contractions were not sustained in non-pregnant myometrium (NP, non-pregnant; TP, term-pregnant). (B) Quinidine (10, 20, and 30 µM) produced concentration-dependent phasic contractions. Tonic contractions were also produced at high concentrations of quinidine in pregnant myometrium. (C) Quinidine was applied to myometrium in the presence of TEA (10 mM). TEA (10 mM) produced strong phasic contractions in non-pregnant myometrium (1.2±0.15 g) but not in pregnant myometrium. Quinidine (10~30 µM), even in the presence of TEA, increased contraction frequency in non-pregnant myometrium and produced stronger contractions in pregnant myometrium.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5015002&req=5

Figure 1: Effect of quinidine on the isometric contraction of uterine longitudinal muscle in mice.(A) Oxytocin (OXT) produced initial and tonic contractions; however, tonic contractions were not sustained in non-pregnant myometrium (NP, non-pregnant; TP, term-pregnant). (B) Quinidine (10, 20, and 30 µM) produced concentration-dependent phasic contractions. Tonic contractions were also produced at high concentrations of quinidine in pregnant myometrium. (C) Quinidine was applied to myometrium in the presence of TEA (10 mM). TEA (10 mM) produced strong phasic contractions in non-pregnant myometrium (1.2±0.15 g) but not in pregnant myometrium. Quinidine (10~30 µM), even in the presence of TEA, increased contraction frequency in non-pregnant myometrium and produced stronger contractions in pregnant myometrium.
Mentions: OXT treatment produced tonic contractions superimposed with phasic contractions. Initial peak contractions induced by OXT were 1.5±0.18 g (non-pregnant, n=48, 38) and 2.1±0.20 g (pregnant, n=32, 38), respectively. Tonic contractions were 0.5±0.07 g (non-pregnant, n=48, 46) and 2.0±0.20 g (pregnant, n=32, 38) (Fig. 1A). Tonic contractions induced by OXT were significantly different in non-pregnant and pregnant myometrial tissues.

View Article: PubMed Central - PubMed

ABSTRACT

Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing K+ channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward K+ current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing K+ channels (TASK-2). NIOK in the presence of K+ channel blockers was inhibited further by TASK inhibitors such as quinidine, bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine and increased immunohistochemical expression of TASK-2. Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in the longitudinal myometrium of mouse. Activation of TASK-2 channels seems to play an essential role for relaxing uterus during pregnancy and it might be one of the alternatives for preventing preterm delivery.

No MeSH data available.


Related in: MedlinePlus