Oxytocin-induced changes in single cell K+ currents and smooth muscle contraction of guinea-pig gastric antrum.
To study the effects of oxytocin on both spontaneous phasic contractions and K+ outward currents (IK) of the so-called 'non-target' smooth muscle cells, physiological concentrations of oxytocin ranging between 10(-12) mol/l and 10(-8) mol/l were applied to smooth muscle preparations and single voltage-clamped cells isolated from the circular layer of the guinea-pig gastric antrum. Oxytocin (10(-12) mol/l to 10(-8) mol/l) suppressed, in a dose-dependent manner, the tetrodotoxin- and atropine-resistant spontaneous phasic contractions and shifted rightward the dose-response curves of 10(-7) mol/l charybdotoxin and 10(-3) mol/l BaCl2. In cells with preloaded intracellular Ca2+ stores, oxytocin (10(-12) mol/l to 10(-9) mol/l) caused a dose-dependent activation of the charybdotoxin-blockable non-inactivating component of IK (IK(sl)) of single voltage-clamped cells, which was accompanied by hyperpolarization of the cell membranes. 8Lys-vasopressin and 8arg-vasopressin failed to mimic the effects of oxytocin on both contraction and K+ currents. Further, the oxytocin-induced activation of IK(sl) was effectively antagonized by 5 x 10(-8) mol/l U-73122 or 5 x 10(-6) mol/l 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate (inhibitors of the cell membrane phospholipase C), as well as by intracellularly applied heparin (selective inhibitor of inositol-1,4,5-trisphosphate (IP3)-induced Ca2+ release channels). In cells incubated in the absence of Ca2+ entry throughout the study, oxytocin (10(-9) mol/l) caused a slight and transient increase of IK(sl) amplitudes. Neither ryanodine (10(-6) mol/l) nor cyclopiazonic acid (10(-6) mol/l) were able to restore the IK-activating effect of oxytocin in these cells. The data obtained suggest (i) that selective oxytocin receptors are present on the membranes of guinea-pig antral smooth muscle cells, (ii) that the oxytocin-related relaxation may result from the activation of Ca(2+)-sensitive K+ conductivity via activation of IP3-induced release of Ca2+ from the submembrane located cisternae of the sarcoplasmic reticulum Ca2+ stores and (iii) in turn, this evokes a non-inactivating component of IK, hyperpolarizing the cell membrane.
Duridanova
D B
DB
Department of Membrane Ion Channels, Institute of Biophysics, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Nedelcheva
M D
MD
Gagov
H S
HS
D000818:Animals; D002118:Calcium / Q000502:physiology; D004553:Electric Conductivity; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D010121:Oxytocin / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology*; D011706:Pyloric Antrum / Q000187:drug effects*; D010738:Type C Phospholipases / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology
D014667:Vasopressins; D010121:Oxytocin; D006493:Heparin; D010738:Type C Phospholipases; D011188:Potassium; D002118:Calcium