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(Circulation Research. 2000;86:e63.)
© 2000 American Heart Association, Inc.

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A Novel Anionic Inward Rectifier in Native Cardiac Myocytes

Dayue Duan, Lingyu Ye, Fiona Britton, Burton Horowitz, Joseph R. Hume

From the Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nev.

Correspondence to Dayue Duan, MD, PhD, Department of Physiology and Cell Biology/351, University of Nevada School of Medicine, Reno, NV 89557-0046. E-mail dduan{at}med.unr.edu

Abstract—Although the cationic inward rectifiers (Kir and hyperpolarization-activated I_f channels) have been well characterized in cardiac myocytes, the expression and physiological role of anionic inward rectifiers in heart are unknown. In the present study, we report the functional and molecular identification of a novel chloride (Cl^-) inward rectifier (Cl.ir) in mammalian heart. Under conditions in which cationic inward rectifier channels were blocked, membrane hyperpolarization (-40 to -140 mV) activated an inwardly rectifying whole-cell current in mouse atrial and ventricular myocytes. Under isotonic conditions, the current activated slowly with a biexponential time course (time constants averaging 179.7±23.4 [mean±SEM] and 2073.6±287.6 ms at -120 mV). Hypotonic cell swelling accelerated the activation and increased the current amplitude whereas hypertonic cell shrinkage inhibited the current. The inwardly rectifying current was carried by Cl^- (I_Cl.ir) and had an anion permeability sequence of Cl^->I^->>aspartate. I_Cl.ir was blocked by 9-anthracene-carboxylic acid and cadmium but not by stilbene disulfonates and tamoxifen. A similar I_Cl.ir was also observed in guinea pig cardiac myocytes. The properties of I_Cl.ir are consistent with currents generated by expression of ClC-2 Cl^- channels. Reverse transcription polymerase chain reaction and Northern blot analysis confirmed transcriptional expression of ClC-2 in both atrial and ventricular tissues and isolated myocytes of mouse and guinea pig hearts. These results indicate that a novel I_Cl.ir is present in mammalian heart and support a potentially important role of ClC-2 channels in the regulation of cardiac electrical activity and cell volume under physiological and pathological conditions. The full text of this article is available at http://www.circresaha.org.

Key Words: channel, Cl^- • action potential • cell volume

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