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Myometrial Calcium and Potassium Channels Play a Pivotal Role in Chromium-Induced Relaxation in Rat Uterus: an In Vitro Study

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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).

Proposed signaling pathway(s) of chromium (VI)-induced myometrial relaxations in rats. KATP: ATP-sensitive K+ channel; KV: voltage-dependent K+ channel; VDCC: voltage-dependent Ca2+ channel; [Ca2+]i: intracellular calcium concentration, stimulatory mechanism, inhibitory mechanism

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Funding

The first author received financial assistance from the Indian Council of Agricultural Research (ICAR), New Delhi, in the form of Senior Research Fellowship (SRF). The research work presented in this MS was supported by the Indian Council of Agriculture Research (ICAR), New Delhi, under Niche Area of Excellence Programme (NAE) to Department of Veterinary Pharmacology and Toxicology, DUVASU, Mathura, India (Grant no: 10(10)/2012-EPD, dated: 23rd March 2012).

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Authors and Affiliations

  1. Smooth Muscle Pharmacology Laboratory, Department of Veterinary Pharmacology & Toxicology, College of Veterinary Science and Animal Husbandry, U.P. Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya, Evam Go-Anusandhan Sansthan (DUVASU), Mathura, 281001, India

    Shirish Bhatiya, Soumen Choudhury, Manju Gari, Pawan Singh, Amit Shukla & Satish Kumar Garg

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  1. Shirish Bhatiya
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  2. Soumen Choudhury
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Correspondence to Satish Kumar Garg.

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All the experimental studies were undertaken after the approval of the Institutional Animal Ethics Committee (IAEC), DUVASU, Mathura, as per the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Gov. of India.

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Bhatiya, S., Choudhury, S., Gari, M. et al. Myometrial Calcium and Potassium Channels Play a Pivotal Role in Chromium-Induced Relaxation in Rat Uterus: an In Vitro Study. Biol Trace Elem Res 198, 198–205 (2020). https://doi.org/10.1007/s12011-020-02041-x

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