Korean J Physiol Pharmacol.  2014 Dec;18(6):503-508. 10.4196/kjpp.2014.18.6.503.

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

• KMID: 2285553
• DOI: http://doi.org/10.4196/kjpp.2014.18.6.503

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 1microM lanthanides (a potent TRPC4/5 stimulator) and suppressed by 10microM 2-APB (TRPC4-7 inhibitor). In addition, in isometric tension experiment, SMC which was evoked by passive stretch was greatly potentiated by lanthanide (1microM) and suppressed by 2-APB (10microM), 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.

Keyword

Osmotic stress; Spontaneous uterine contraction; Stretch; Transient receptor potential C4/5

MeSH Terms

Animals
Female
Gestational Age
Humans
Lanthanoid Series Elements
Mice
Muscle Cells
Myometrium
Obstetric Labor, Premature
Osmotic Pressure
Patch-Clamp Techniques
Pregnancy
Rats*
Uterine Contraction*
Uterus
Lanthanoid Series Elements

Figure

• 

  Fig. 1 Hypoosmotic swelling-induced outward rectifying current in rat pregnant myocyte. (A) A representative trace of whole cell current induced by hypoosmotic swelling. Membrane potential of myocyte was held at -60 mV. (B) I~V relationship of hypoosmotic swelling-induced current. The current was obtained from the same cell as in (A). (C) Summary of normalized amplitude of hypoosmotic swelling-induced current. The current amplitudes in each groups were measured at -60 and +60 mV respecvtively. *p<0.05, **p<0.01, ***p<0.001.

• 

  Fig. 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.

• 

  Fig. 3 Effects of Lanthanides and 2-APB on Ihypo. (A) Left, I~V relationship of Ihypo in presence of Gd3+ and Gd3+ plus 2-APB. Right, summary of effects for Gd3+ and Gd3+ plus 2-APB on Ihypo. (B) Left, I~V relationship of Ihypo in presence of La3+ and La3+ plus 2-APB. Right, summary of effects for La3+ and La3+ plus 2-APB on Ihypo. *p<0.05, **p<0.01, ***p<0.001.

• 

  Fig. 4 Effects of Lanthanide and 2-APB on stretch-induced contraction in rat pregnant myometrium. (A) Left, a representative trace of augmenting effect of 1µM Gd3+ on SMC and effect of 2-APB on the augmenting effect of Gd3+. Right, a representative trace of augmenting effect of 1µM La3+ on SMC and effect of 2-APB on the augmenting effect of La3+ (B) Left, summary of effects for Gd3+ and Gd3+ plus 2-APB on mean frequency and amplitude of SMC. Right, summary of effects for La3+ and La3+ plus 2-APB on mean frequency and amplitude of SMC. **p<0.01.

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