Pharmacological and Biophysical Properties of Swelling-Activated Chloride Channel in Mouse Cardiac Myocytes

Jun Wang；Hong-Tao Xu；Xi-Qing Sun；Wei-Zhen Niu

cardiac myocytes ； cell volume regulation ； swelling-activated Cl(superscript -) channel ； patch clamp

The Chinese Journal of Physiology

49卷3期（2006 / 06 / 30）

126 - 131

英文

The present study was designed to observe the properties of swelling-activated chloride channel (I(subscript CLswell) in mouse cardiac myocytes using patch clamp techniques. In whole-cell recordings, hypotonic solution activated a chloride current that exhibited outward rectification, weak voltage-dependent inactivation, and anion selectivity with permeability sequence of I(superscript -)＞ Br(superscript -)＞Cl(superscript -). The current was sensitive to Cl(superscript -) channel blockers tamoxifen, NPPB and DIDS. In single-channel recordings, cell swelling activated a single channel current which showed outward rectification with open probability of 0.76±0.08 and conductance of 38.1±2.5pS at +100mV under [Cl(superscript -)] symmetrical condition. I-V relation revealed the reversal potential as expected for a Cl(superscript -)-selective channel. These results suggested that in mouse cardiac myocytes, swelling-activated, outward rectifying chloride channel with a single channel conductance of 38.1±2.5pS (at +100mV under [Cl(superscript -)] symmetrical condition) underlies the volume regulatory Cl(superscript -) channel.

1. Ackerman, M.J.,Clapham, D.E.(1993).Cardiac chloride channels.Trends. Cardiovasc. Med.,3,23-28.
2. Baumgarten, C.M.,Clemo, H.F.(2003).Swelling-activated chloride channels in cardiac physiology and pathophysiology.Prog. Biophys. Mol. Biol.,82,25-42.
3. Benitah, J.P.,Gomez, A.M.,Delgado, C.,Lorente, P.,Lederer, W.J.(1997).A chloride current component induced by hypertrophy in rat ventricular myocytes..Am. J. Physiol.,272,2500-2506.
4. Bouron, A.,Potreau, D.,Raymond, G.(1991).Possible involvement of a chloride conductance in the transient outward current of wholecell voltage-clamped ferret ventricular myocytes.Pflugers. Arch,419,534-536.
5. Garber, S.,Cahalan, M.D.(1997).Volume-regulated anion channels and the control of a simple cell behavior.Cell. Physiol. Biochem.,7,229-241.
6. Gopal, R.,Ten Eick, E.R.(1997).Cytochalasin D alters relationship between swelling-activated chloride current and cardiac myocyte size (Abstract).Biophys. J.,72,226.
7. Hagiwara, N.,Masuda, H.,Shoda, M.,Irisawa, H.(1992).Stretchactivated anion currents of rabbit cardiac myocytes.J. Physiol.,456,285-302.
8. Hiraoka, M.,Kawano, S.,Hirano, Y.,Furukawa, T.(1998).Role of cardiac chloride currents in changes in action potential characteristics and arrhythmias.Cardiovasc. Res.,40,23-33.
9. Jennings, R.B.,Reimer, K.A.,Steenbergen, C.(1986).Myocardial ischemia revisited, the osmolar load, membrane damage, and reperfusion..J. Mol. Cell. Cardiol.,18,769-780.
10. Nilius, B.,Eggermont, J.,Voets, T.,Buyse, G.,Manolopoulos, V.,Droogmans, G.(1997).Properties of volume-regulated anion channels in mammalian cells..Prog. Biophys. Mol. Biol.,68,69-119.
11. Okada, Y.,Hazama, A.(1989).Volume-regulatory ion channel in epithelial cells..News Physiol. Sci.,4,238-242.
12. Okada, Y.,Maeno, E.,Shimizu, T.,Dezaki, K.,Wang, J.,Morishima, S.(2001).Receptor-mediated control of regulatory volume decrease (RVD) and apoptotic volume decrease (AVD)..J. Physiol,532,3-16.
13. Okada,Y.(1997).Volume expansion-sensing outward-rectifier Cl(superscript -) channel: fresh start to the molecular identity and volume sensor.Am. J. Physiol.,273,755-789.
14. Oz, M.C.,Sorota, S.(1995).Forskolin stimulates swelling-induced chloride current, not cardiac cystic fibrosis transmembrane-conductance regulator current, in human cardiac myocytes.Circ. Res,76,1063-1070.
15. Rasmusson, R.L.,Davis, D.G.,Lieberman, M.(1993).Amino acid loss during volume regulatory decrease in cultured chick heart cells.Am. J. Physiol.,264,136-145.
16. Shen, M.R.,Droogmans, G.,Eggermont, J.,Voets, T.,Ellory, J.C.,Nilius B.(2000).Differential expression of volume-regulated anion channels during cell cycle progression of human cervical cancer cells..J. Physiol.,529,385-395.
17. Sorota, S.(1992).Swelling-induced chloride-sensitive current in canine atrial cells revealed by whole-cell patch-clamp method.Circ. Res,70,679-687.
18. Sorota, S.(1994).Pharmacologic properties of the swelling-induced chloride current of dog atrial myocytes.J. Cardiovasc. Electrophysiol,5,1006-1016.
19. Strange, K.,Emma, F.,Jackson, P.S.(1996).Cellular and molecular physiology of volume-sensitive anion channels.Am. J. Physiol,270,711-730.
20. Tseng, G.N.(1992).Cell swelling increases membrane conductance of canine cardiac cells: evidence for a volume-sensitive Cl(superscript -) channel.Am. J. Physiol,262,1056-1068.
21. Vandenberg, J.I.,Yoshida, A.,Kirk, K.,Powell, T.(1994).Swellingactivated and isoprenaline-activated chloride currents in guinea pig cardiac myocytes have distinct electrophysiology and pharmacology..J. Gen. Physiol.,104,997-1017.
22. Wolska, B.M.,Solaro, R.J.(1996).Method for isolation of adult mouse cardiac myocytes for studies of contraction and microfluorimetry.Am. J. Physiol.,271,1250-1255.
23. Wondergem, R.,Gong, W.,Monen, S.H.,Dooley, S.N.,Gonce, J.L.,Conner, T.D.,Houser, M.,Ecay, T.W.,Ferslew, K.E.(2001).Blocking swelling-activated chloride current inhibits mouse liver cell proliferation.J. Physiol.,532,661-672.
24. Wright, A.R.,Rees, S.A.(1997).Targeting ischemia-cell swelling and drug efficacy.Trends. Pharmacol. Sci.,18,224-228.
25. Zygmunt, A.C.,Gibbons, W.R.(1992).Properties of the calciumactivated chloride current in the heart.J. Gen. Physiol.,99,391-414.