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Oxytocin actions on voltage-dependent ionic channels in pregnant rat uterine smooth muscle cells
Y Inoue1, K Shimamura, N Sperelakis
1Department of Physiology and Biophysics, College of Medicine, University of Cincinnati, Ohio 45267-0576.
Abstract:
The effects of oxytocin, a uterotonic polypeptide hormone, on the voltage-dependent slow calcium, fast sodium, and potassium channel currents were studied using whole-cell voltage clamp of freshly isolated cells from late pregnant (18-21 day) rat myometrium. The calcium current was rapidly inhibited by oxytocin (about 25% inhibition at 20 nM) in a dose-dependent manner, and this inhibitory effect was completely reversible by washout. However, inhibition was not observed when barium was used as the charge carrier. Sodium current and potassium current were not modified by oxytocin, thus sodium and potassium currents may not play important roles in oxytocin-induced augmentation of uterine contraction. It is concluded that oxytocin stimulates uterine contraction by mechanisms other than augmentation of the voltage-dependent calcium current, e.g., by release of Ca from sarcoplasmic reticulum (by inositol triphosphate) or by activation of a receptor-operated Ca channel. The inhibition of the slow calcium current may be induced by the elevation of [Ca]i.
Insights
Oxytocin, a hormone that stimulates uterine contractions, inhibits slow calcium channels in rat myometrium. This effect on calcium channels, not sodium or potassium channels, may explain how oxytocin enhances uterine activity.
Area of Science:
- Physiology
- Pharmacology
- Reproductive Biology
Background:
- Oxytocin is a key hormone regulating uterine contractions during labor.
- The precise ionic mechanisms underlying oxytocin's action on myometrium are not fully elucidated.
- Voltage-dependent ion channels play critical roles in smooth muscle excitability.
Purpose of the Study:
- To investigate the effects of oxytocin on voltage-dependent ion channel currents in rat myometrium.
- To determine the role of calcium, sodium, and potassium currents in oxytocin-mediated uterine contractions.
Main Methods:
- Whole-cell voltage clamp technique was employed.
- Freshly isolated myometrial cells from late pregnant rats (18-21 days) were used.
- Effects of oxytocin on calcium, sodium, and potassium currents were assessed.
Main Results:
- Oxytocin rapidly and dose-dependently inhibited the slow calcium current (approx. 25% at 20 nM).
- This inhibition of calcium current by oxytocin was fully reversible.
- Oxytocin did not affect sodium or potassium currents.
- Inhibition of calcium current by oxytocin was not observed when using barium as the charge carrier.
Conclusions:
- Oxytocin stimulates uterine contraction through mechanisms independent of augmenting voltage-dependent calcium current.
- Oxytocin may induce uterine contraction via calcium release from the sarcoplasmic reticulum or activation of receptor-operated calcium channels.
- The observed inhibition of slow calcium current by oxytocin might be mediated by intracellular calcium ([Ca]i) elevation.
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