Myometrial Calcium and Potassium Channels Play a Pivotal Role in Chromium-Induced Relaxation in Rat Uterus: an In Vitro
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Myometrial Calcium and Potassium Channels Play a Pivotal Role in Chromium-Induced Relaxation in Rat Uterus: an In Vitro Study Shirish Bhatiya 1 & Soumen Choudhury 1 & Manju Gari 1 & Pawan Singh 1 & Amit Shukla 1 & Satish Kumar Garg 1 Received: 19 November 2019 / Accepted: 7 January 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Hexavalent chromium, a well-known environmental toxicant, adversely affects female reproduction and results in abnormal implantation, fetal resorption, and reduction in litter size. Uterine myogenic activity is under control of number of receptors and ion channels, and it regulates fetal-implantation and feto-maternal communication. Despite several known adverse effects of chromium on female reproduction, direct action of chromium on myometrial activity is yet to be understood. In the present study, the effect of in vitro exposure of hexavalent chromium (Cr-VI) on the myogenic activity of isolated myometrial strips of rats was evaluated after mounting the tissue in thermostatically (37 ± 0.5 °C) controlled organ bath under a resting tension of 1 g. Chromium produced concentration-dependent (0.1 nM–0.1 mM) inhibitory effect on myometrial activity. Following pre-treatment of the myometrial strips with glibenclamide (a KATP channel blocker) and 4-aminopyridine (a Kv channel blocker), the concentration– response curve (CRC) of chromium was significantly (P < 0.05) shifted towards right with decrease in the maximum relaxant effect. Contractile effects of CaCl2 and BAY K-8644 (a selective opener of L-type Ca2+ channel) were significantly (P < 0.05) attenuated in the presence of chromium. Chromium-induced myometrial relaxation was also significantly (P < 0.05) reduced in the presence of ICI 118,551 (a selective β2-antagonist) and SR 59230A (a selective β3-antagonist). These findings evidently suggest that chromium produced relaxant effect on rat myometrium by interfering with Ca2+ entry through voltage-dependent Ca2+ channels, and by interacting with beta-adrenoceptors (β2 and β3) and potassium channels (especially KATP and Kv channels). Keywords Chromium . L-type calcium channel . Potassium channel . β-Adrenoceptors . Uterus
Introduction Human beings and animals are being inadvertently exposed to chromium through inhalation, ingestion of food and feed/fodder, and drinking water [1–4]. Chromium (Cr) is the 21st most abundant element in earth crust and is one of the eight metals in top priority list of the toxic substances [5]. Chromium compounds are mainly found in two forms, i.e., trivalent chromium (Cr-III) and hexavalent chromium (Cr-VI) in earth crust. Chromium (Cr-III) is an essential micronutrient as well and increases insulin production by increasing insulin binding and sensitivity [6]. It is relatively insoluble in water
* Satish Kumar Garg [email protected]; [email protected] 1
Smooth Muscle Pharmacology Laboratory, Department of Veterinary Pharmacology & Toxicology, College of Veterinary Science and Animal Husbandry, U.P. Pandit D
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