Expression of HERG in CD1 Mice Gallbladder and Its Possible Implications_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SUN Xiaomin ¹ , YU Baoping ² , GAO Liceng ¹ , XU Long ² , DONG Weiguo ² , LUO Hesheng ² , XU Ping ¹

1.Department of Gastroenterology, Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 201600, China;;
2.Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan 430060, China Corresponding Author: YU Bao-ping, E-mail: yubaoping62@yahoo.com.cn;

Corresponding author：

Keywords：

Human ether-a-go-go related gene; Gallbladder; Tyrosine kinase receptor; CD1 mice

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Objective 　To study the expressions of human ether-a-go-go related gene (HERG) in CD1 mice gallbladder and interstitial cells of Cajal (ICC) and explore their possible implications.
Methods 　The expression of HERG protein in gallbladder tissue slices obtained from CD1 mice was detected by immunohistochemistry method. The expression of HERG mRNA in gallbladder tissue was detected by reverse transcription (RT)-PCR. The production of HERG protein was confirmed in the CD1 mice gallbladder by Western blot. Enzymatically dispersed cells were identified as ICC using the specific ICC marker c-kit antibody, and the double positive cells of c-kit and HERG were observed by laser passing confocal microscope.
Results 　HERG was present in the CD1 mice gallbladder tissues for the yellow or buffy positive reaction. At the same time, the expression of mRNA specific for the HERG gene and production of HERG protein in the CD1 mice gallbladder tissues were indicated by RT-PCR and Western blot analysis, respectively. Using double labeling of anti-c-kit and anti-HERG, the double positive cells of c-kit and HERG were observed in the CD1 mice ICC by laser passing confocal microscope.
Conclusion 　The study demonstrates that HERG is present in the CD1 mice gallbladder tissues and ICC, which is likely related to the pacemaking activity of ICC.

Citation： SUN Xiaomin,YU Baoping,GAO Liceng,XU Long,DONG Weiguo,LUO Hesheng,XU Ping. Expression of HERG in CD1 Mice Gallbladder and Its Possible Implications. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(9): 740-744. doi: Copy

1.	Parr E, Pozo MJ, Horowitz B, et al. ERG K+ channels modulate the electrical and contractile activities of gallbladder smooth muscle [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2003; 284(3): G392-G398.
2.	Pillozzi S, Brizzi MF, Balzi M, et al. HERG potassium cha-nnels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors [Ｊ]. Leukemia, 2002; 16(9): 1791-1798.
3.	Lastraioli E, Guasti L, Crociani O, et al. herg1 gene and HERG1 protein are overexpressed in colorectal cancers and regulate cell invasion of tumor cells [Ｊ]. Cancer Res, 2004; 64(2): 606-611.
4.	Farrelly AM, Ro S, Callaghan BP, et al. Expression and function of KCNH2 (HERG) in the human jejunum [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2003; 284(6): G883-G895.
5.	Imai T, Okamoto T, Yamamoto Y, et al. Effects of different types of K+ channel modulators on the spontaneous myogenic contraction of guinea-pig urinary bladder smooth muscle [Ｊ]. Acta Physiol Scand, 2001; 173(3): 323-333.
6.	Ohya S, Asakura K, Muraki K, et al. Molecular and functional characterization of ERG, KCNQ, and KCNE subtypes in rat stomach smooth muscle [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2002; 282(2): G277-G287.
7.	Zhu Y, Golden CM, Ye J, et al. ERG K+ currents regulate pacemaker activity in ICC [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2003; 285(6): G1249-G1258.
8.	Zhu Y, Ye J, Huizinga JD. Clotrimazole-sensitive K+ currents regulate pacemaker activity in interstitial cells of Cajal [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2007; 292(6): G1715-G1725.
9.	孙晓敏, 余保平, 高礼层, 等. 小鼠胆囊Cajal间质细胞的初步研究 [Ｊ]. 中华消化杂志, 2007; 27(4): 225-227.
10.	Schwarz JR, Bauer CK. Functions of erg K+ channels in excitable cells [Ｊ]. J Cell Mol Med, 2004; 8(1): 22-30.
11.	Hua F, Johns DC, Gilmour RF Jr. Suppression of electrical alternans by overexpression of HERG in canine ventricular myocytes [Ｊ]. Am J Physiol Heart Circ Physiol, 2004; 286(6): H2342-H2351.
12.	Volberg WA, Koci BJ, Su W, et al. Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics [Ｊ]. J Pharmacol Exp Ther, 2002; 302(1): 320-327.
13.	Akbarali HI, Thatte H, He XD, et al. Role of HERG-like K+ currents in opossum esophageal circular smooth muscle [Ｊ]. Am J Physiol, 1999; 277(6 Pt 1): C1284-C1290.
14.	Everson GT. Gallbladder function in gallstone disease [Ｊ]. Gastroenterol Clin North Am, 1991; 20(1): 85-110.
15.	别平, 范毓东. 胆囊结石发病机理的研究进展 [Ｊ]. 中国普外基础与临床杂志, 2003; 10(5): 439-441.
16.	Konturek JW, Scott GW, Kingma YJ. Electrical activity of canine gallbladder [Ｊ]. Physiol Pharmacol, 1991; 42(1): 85-91.
17.	Ward SM, Ordg T, Bayguinov JR, et al. Development of interstitial cells of Cajal and pacemaking in mice lacking enteric nerves [Ｊ]. Gastroenterology, 1999; 117(3): 584-594.
18.	Wu JJ, Rothman TP, Gershon MD. Development of the interstitial cell of Cajal: origin, kit dependence and neuronal and nonneuronal sources of kit ligand [Ｊ]. J Neurosci Res, 2000; 59(3): 384-401.
19.	Vanderwinden JM, Rumessen JJ, Bernex F， et al. Distribution and ultrastructure of interstitial cells of Cajal in the mouse colon, using antibodies to Kit and Kit (W-lacZ) mice [Ｊ]. Cell Tissue Res, 2000; 302: 155-170.
20.	Ward SM, Sanders KM. Interstitial cells of Cajal: primary targets of enteric motor innervation [Ｊ]. Anat Rec, 2001; 262(1): 125-135.
21.	Ward SM, Sanders KM. Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside. Ⅰ. Functional development and plasticity of interstitial cells of Cajal networks [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2001; 281(3): G602-G611.

1. Parr E, Pozo MJ, Horowitz B, et al. ERG K+ channels modulate the electrical and contractile activities of gallbladder smooth muscle [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2003; 284(3): G392-G398.
2. Pillozzi S, Brizzi MF, Balzi M, et al. HERG potassium cha-nnels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors [Ｊ]. Leukemia, 2002; 16(9): 1791-1798.
3. Lastraioli E, Guasti L, Crociani O, et al. herg1 gene and HERG1 protein are overexpressed in colorectal cancers and regulate cell invasion of tumor cells [Ｊ]. Cancer Res, 2004; 64(2): 606-611.
4. Farrelly AM, Ro S, Callaghan BP, et al. Expression and function of KCNH2 (HERG) in the human jejunum [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2003; 284(6): G883-G895.
5. Imai T, Okamoto T, Yamamoto Y, et al. Effects of different types of K+ channel modulators on the spontaneous myogenic contraction of guinea-pig urinary bladder smooth muscle [Ｊ]. Acta Physiol Scand, 2001; 173(3): 323-333.
6. Ohya S, Asakura K, Muraki K, et al. Molecular and functional characterization of ERG, KCNQ, and KCNE subtypes in rat stomach smooth muscle [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2002; 282(2): G277-G287.
7. Zhu Y, Golden CM, Ye J, et al. ERG K+ currents regulate pacemaker activity in ICC [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2003; 285(6): G1249-G1258.
8. Zhu Y, Ye J, Huizinga JD. Clotrimazole-sensitive K+ currents regulate pacemaker activity in interstitial cells of Cajal [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2007; 292(6): G1715-G1725.
9. 孙晓敏, 余保平, 高礼层, 等. 小鼠胆囊Cajal间质细胞的初步研究 [Ｊ]. 中华消化杂志, 2007; 27(4): 225-227.
10. Schwarz JR, Bauer CK. Functions of erg K+ channels in excitable cells [Ｊ]. J Cell Mol Med, 2004; 8(1): 22-30.
11. Hua F, Johns DC, Gilmour RF Jr. Suppression of electrical alternans by overexpression of HERG in canine ventricular myocytes [Ｊ]. Am J Physiol Heart Circ Physiol, 2004; 286(6): H2342-H2351.
12. Volberg WA, Koci BJ, Su W, et al. Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics [Ｊ]. J Pharmacol Exp Ther, 2002; 302(1): 320-327.
13. Akbarali HI, Thatte H, He XD, et al. Role of HERG-like K+ currents in opossum esophageal circular smooth muscle [Ｊ]. Am J Physiol, 1999; 277(6 Pt 1): C1284-C1290.
14. Everson GT. Gallbladder function in gallstone disease [Ｊ]. Gastroenterol Clin North Am, 1991; 20(1): 85-110.
15. 别平, 范毓东. 胆囊结石发病机理的研究进展 [Ｊ]. 中国普外基础与临床杂志, 2003; 10(5): 439-441.
16. Konturek JW, Scott GW, Kingma YJ. Electrical activity of canine gallbladder [Ｊ]. Physiol Pharmacol, 1991; 42(1): 85-91.
17. Ward SM, Ordg T, Bayguinov JR, et al. Development of interstitial cells of Cajal and pacemaking in mice lacking enteric nerves [Ｊ]. Gastroenterology, 1999; 117(3): 584-594.
18. Wu JJ, Rothman TP, Gershon MD. Development of the interstitial cell of Cajal: origin, kit dependence and neuronal and nonneuronal sources of kit ligand [Ｊ]. J Neurosci Res, 2000; 59(3): 384-401.
19. Vanderwinden JM, Rumessen JJ, Bernex F， et al. Distribution and ultrastructure of interstitial cells of Cajal in the mouse colon, using antibodies to Kit and Kit (W-lacZ) mice [Ｊ]. Cell Tissue Res, 2000; 302: 155-170.
20. Ward SM, Sanders KM. Interstitial cells of Cajal: primary targets of enteric motor innervation [Ｊ]. Anat Rec, 2001; 262(1): 125-135.
21. Ward SM, Sanders KM. Physiology and pathophysiology of the interstitial cell of Cajal: from bench to bedside. Ⅰ. Functional development and plasticity of interstitial cells of Cajal networks [Ｊ]. Am J Physiol Gastrointest Liver Physiol, 2001; 281(3): G602-G611.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of HERG in CD1 Mice Gallbladder and Its Possible Implications

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