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Transient receptor potential c4/5 like channel is involved in stretch-induced spontaneous uterine contraction of pregnant rat.

Chung S, Kim YH, Joeng JH, Ahn DS - Korean J. Physiol. Pharmacol. (2014)

Bottom Line: In human and rat uterus, all TRPCs except TRPC2 are expressed in pregnant myometrium and among them, TRPC4 are predominant throughout gestation, suggesting a possible role in regulation of SMC.The current was significantly potentiated by 1µM lanthanides (a potent TRPC4/5 stimulator) and suppressed by 10µM 2-APB (TRPC4-7 inhibitor).These results provide a possible cellular mechanism for regulation of SMC during pregnancy and provide basic information for developing a new agent for treatment of premature labor.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea.

ABSTRACT
Spontaneous myometrial contraction (SMC) in pregnant uterus is greatly related with gestational age and growing in frequency and amplitude toward the end of gestation to initiate labor. But, an accurate mechanism has not been elucidated. In human and rat uterus, all TRPCs except TRPC2 are expressed in pregnant myometrium and among them, TRPC4 are predominant throughout gestation, suggesting a possible role in regulation of SMC. Therefore, we investigated whether the TRP channel may be involved SMC evoked by mechanical stretch in pregnant myometrial strips of rat using isometric tension measurement and patch-clamp technique. In the present results, hypoosmotic cell swelling activated a potent outward rectifying current in G protein-dependent manner in rat pregnant myocyte. The current was significantly potentiated by 1µM lanthanides (a potent TRPC4/5 stimulator) and suppressed by 10µM 2-APB (TRPC4-7 inhibitor). In addition, in isometric tension experiment, SMC which was evoked by passive stretch was greatly potentiated by lanthanide (1µM) and suppressed by 2-APB (10µM), suggesting a possible involvement of TRPC4/5 channel in regulation of SMC in pregnant myometrium. These results provide a possible cellular mechanism for regulation of SMC during pregnancy and provide basic information for developing a new agent for treatment of premature labor.

No MeSH data available.


Related in: MedlinePlus

Effect of GDPβS on Ihypo. (A) Left, Ihypo was recorded in rat pregnant myocyte. The representative I~V relationships of Ihypo by voltage ramp of -100 to 100 mV during 500-ms durations. Right, summary of normalized amplitude of Ihypo. The current amplitudes in each group were measured at -60 and +60 mV respectively. (B) A representative trace of Ihypo in the presence of GDPβS (2 mM) in pipette solution. Hypoosmotic solution was applied to pregnant rat myocyte after 7 min dialysis with GDPβS in the pipette solution. Right, summary of normalized amplitude of Ihypo. The current amplitudes in each group were measured at -60 and +60 mV respectively. (A) *p<0.05, **p<0.01. (B) p>0.05.
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Figure 2: Effect of GDPβS on Ihypo. (A) Left, Ihypo was recorded in rat pregnant myocyte. The representative I~V relationships of Ihypo by voltage ramp of -100 to 100 mV during 500-ms durations. Right, summary of normalized amplitude of Ihypo. The current amplitudes in each group were measured at -60 and +60 mV respectively. (B) A representative trace of Ihypo in the presence of GDPβS (2 mM) in pipette solution. Hypoosmotic solution was applied to pregnant rat myocyte after 7 min dialysis with GDPβS in the pipette solution. Right, summary of normalized amplitude of Ihypo. The current amplitudes in each group were measured at -60 and +60 mV respectively. (A) *p<0.05, **p<0.01. (B) p>0.05.

Mentions: We determined the involvement of G proteins in activation of IHypo using GDPβS, a hydrolysis-resistant GDP analogue known to prevent G protein activation [20]. As shown in Fig. 2B, intracellular dialysis of GDPβS (2 mM) prevented induction of IHypo (5.3±1.0 pA/pF for 300 mOsm, 6.7±1.9 pA/pF for 220 mOsm at -60 mV; 5.3±1.0 pA/pF for 300 mOsm, 5.9±0.9 pA/pF for 220 mOsm, n=5, p>0.05). These results suggest that G-protein may be involved in activation of IHypo in rat pregnant myometrium.


Transient receptor potential c4/5 like channel is involved in stretch-induced spontaneous uterine contraction of pregnant rat.

Chung S, Kim YH, Joeng JH, Ahn DS - Korean J. Physiol. Pharmacol. (2014)

Effect of GDPβS on Ihypo. (A) Left, Ihypo was recorded in rat pregnant myocyte. The representative I~V relationships of Ihypo by voltage ramp of -100 to 100 mV during 500-ms durations. Right, summary of normalized amplitude of Ihypo. The current amplitudes in each group were measured at -60 and +60 mV respectively. (B) A representative trace of Ihypo in the presence of GDPβS (2 mM) in pipette solution. Hypoosmotic solution was applied to pregnant rat myocyte after 7 min dialysis with GDPβS in the pipette solution. Right, summary of normalized amplitude of Ihypo. The current amplitudes in each group were measured at -60 and +60 mV respectively. (A) *p<0.05, **p<0.01. (B) p>0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4296040&req=5

Figure 2: Effect of GDPβS on Ihypo. (A) Left, Ihypo was recorded in rat pregnant myocyte. The representative I~V relationships of Ihypo by voltage ramp of -100 to 100 mV during 500-ms durations. Right, summary of normalized amplitude of Ihypo. The current amplitudes in each group were measured at -60 and +60 mV respectively. (B) A representative trace of Ihypo in the presence of GDPβS (2 mM) in pipette solution. Hypoosmotic solution was applied to pregnant rat myocyte after 7 min dialysis with GDPβS in the pipette solution. Right, summary of normalized amplitude of Ihypo. The current amplitudes in each group were measured at -60 and +60 mV respectively. (A) *p<0.05, **p<0.01. (B) p>0.05.
Mentions: We determined the involvement of G proteins in activation of IHypo using GDPβS, a hydrolysis-resistant GDP analogue known to prevent G protein activation [20]. As shown in Fig. 2B, intracellular dialysis of GDPβS (2 mM) prevented induction of IHypo (5.3±1.0 pA/pF for 300 mOsm, 6.7±1.9 pA/pF for 220 mOsm at -60 mV; 5.3±1.0 pA/pF for 300 mOsm, 5.9±0.9 pA/pF for 220 mOsm, n=5, p>0.05). These results suggest that G-protein may be involved in activation of IHypo in rat pregnant myometrium.

Bottom Line: In human and rat uterus, all TRPCs except TRPC2 are expressed in pregnant myometrium and among them, TRPC4 are predominant throughout gestation, suggesting a possible role in regulation of SMC.The current was significantly potentiated by 1µM lanthanides (a potent TRPC4/5 stimulator) and suppressed by 10µM 2-APB (TRPC4-7 inhibitor).These results provide a possible cellular mechanism for regulation of SMC during pregnancy and provide basic information for developing a new agent for treatment of premature labor.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea.

ABSTRACT
Spontaneous myometrial contraction (SMC) in pregnant uterus is greatly related with gestational age and growing in frequency and amplitude toward the end of gestation to initiate labor. But, an accurate mechanism has not been elucidated. In human and rat uterus, all TRPCs except TRPC2 are expressed in pregnant myometrium and among them, TRPC4 are predominant throughout gestation, suggesting a possible role in regulation of SMC. Therefore, we investigated whether the TRP channel may be involved SMC evoked by mechanical stretch in pregnant myometrial strips of rat using isometric tension measurement and patch-clamp technique. In the present results, hypoosmotic cell swelling activated a potent outward rectifying current in G protein-dependent manner in rat pregnant myocyte. The current was significantly potentiated by 1µM lanthanides (a potent TRPC4/5 stimulator) and suppressed by 10µM 2-APB (TRPC4-7 inhibitor). In addition, in isometric tension experiment, SMC which was evoked by passive stretch was greatly potentiated by lanthanide (1µM) and suppressed by 2-APB (10µM), suggesting a possible involvement of TRPC4/5 channel in regulation of SMC in pregnant myometrium. These results provide a possible cellular mechanism for regulation of SMC during pregnancy and provide basic information for developing a new agent for treatment of premature labor.

No MeSH data available.


Related in: MedlinePlus