title: Mechanism underlying hypokalemia induced by trimethyltin chloride: Inhibition of H+/K+-ATPase in renal intercalated cells.
abstract: Trimethyltin chloride (TMT), a byproduct of plastic stabilizers, has caused 67 poisoning accidents in the world; more than 98% (1814/1849) of the affected patients since 1998 have been in China. As a long-established toxic chemical, TMT severely affects the limbic system and the cerebellum; however, its relationship with hypokalemia, a condition observed in the majority of the cases in the last decade, remains elusive. To understand the mechanism underlying hypokalemia induced by TMT, Sprague-Dawley (SD) rats were administered TMT to determine the relationship between H(+)/K(+)-ATPase activity and the blood and urine K(+) concentration and pH, respectively. H(+)/K(+)-ATPase protein and mRNA were observed too. In vitro changes to intracellular pH, K(+) channels in renal cells were measured. The results showed that TMT increased potassium leakage from the kidney, raised urine pH, and inhibited H(+)/K(+)-ATPase activity both in vitro and in vivo. In the tested animals, H(+)/K(+)-ATPase activity was positively correlated with the decrease of plasma K(+) and blood pH but was negatively correlated with the increase of urine K(+) and urine pH (P<0.01), while TMT did not change the expression of H(+)/K(+)-ATPase protein and mRNA. TMT decreased intracellular pH and opened K(+) channels in renal intercalated cells. Our findings suggest TMT can directly inhibit the activity of H(+)/K(+)-ATPases in renal intercalated cells, reducing urine K(+) reabsorption and inducing hypokalemia.
authors.affiliation: Guangdong Poison Control Center, 68 Haikang St. Xingangxi Rd., Guangzhou, 510300, China. river-t@163.com <river-t@163.com>
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Tang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yang
authors.forename: Guanchao
authors.initials: G
authors.lastname: Lai
authors.forename: Jinhui
authors.initials: J
authors.lastname: Guo
authors.forename: Lihua
authors.initials: L
authors.lastname: Xia
authors.forename: Banghua
authors.initials: B
authors.lastname: Wu
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Xie
authors.forename: Ming
authors.initials: M
authors.lastname: Huang
authors.forename: Jiabin
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Ruan
authors.forename: Gang
authors.initials: G
authors.lastname: Sui
authors.forename: Yichen
authors.initials: Y
authors.lastname: Ge
authors.forename: Wulin
authors.initials: W
authors.lastname: Zuo
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.forename: Guanghua
authors.initials: G
authors.lastname: Zhu
authors.forename: Jinxin
authors.initials: J
authors.lastname: Zhang
authors.forename: Laiyu
authors.initials: L
authors.lastname: Li
authors.forename: Wenliang
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007008:Hypokalemia / Q000139:chemically induced* / Q000201:enzymology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000201:enzymology; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000201:enzymology*; D011188:Potassium / Q000097:blood / Q000652:urine; D054328:Proton Pump Inhibitors; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014298:Trimethyltin Compounds / Q000633:toxicity*
chemical_list: D054328:Proton Pump Inhibitors; D012333:RNA, Messenger; D014298:Trimethyltin Compounds; C040533:trimethyltin chloride; D017506:H(+)-K(+)-Exchanging ATPase; D011188:Potassium