Oxytocin-induced changes in single cell K+ currents and smooth muscle contraction of guinea-pig gastric antrum

• Published in: European journal of endocrinology Vol. 136; no. 5; pp. 531 - 538
• Main Authors: DURIDANOVA, D. B, NEDELCHEVA, M. D, GAGOV, H. S
• Format: Journal Article
• Language: English
• Published: Colchester Portland Press 01.05.1997
• Subjects: Animals; Biological and medical sciences; Calcium - physiology; Electric Conductivity; EXPERIMENTAL STUDIES; Fundamental and applied biological sciences. Psychology; Gastrointestinal Motility - drug effects; Guinea Pigs; Heparin - pharmacology; In Vitro Techniques; Muscle, Smooth - cytology; Muscle, Smooth - physiology; Oxytocin - pharmacology; Patch-Clamp Techniques; Potassium - physiology; Pyloric Antrum - drug effects; Stomach; Type C Phospholipases - metabolism; Vasopressins - pharmacology; Vertebrates: digestive system; Animal model; Oxytocin; Potassium ion; Peptide hormone; Rodentia; Neuroendocrine regulation; Isometric muscular contraction; Exploration; Smooth muscle; Ionic current; Neuropeptide; Muscle contraction; Myocyte; Vertebrata; Antrum pyloricum; Mammalia; Guinea pig; Animal; Neurohypophyseal hormone; Biological effect; Mechanism of action
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/eje.0.1360531

Abstract 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 (10−12mol/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 10−3mol/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(s1)) 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(s1) was effectively antagonized by 5× 10−8 mol/l U-73122 or 5× 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(s1) 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 Ca2+-sensitive K+ conductivity via activation of IP3-induced release of Ca 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. European Journal of Endocrinology 136 531–538