A Novel Anionic Inward Rectifier in Native Cardiac Myocytes

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

doi:10.1161/01.res.86.4.e63

Cited by 68 publications

(103 citation statements)

References 70 publications

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“…These properties of I Cl,acid are totally or partially different from those of other cardiac Cl Ϫ currents (I Cl,CFTR , I Cl,vol , I Cl,Ca , and I Cl,ir ) identified so far. I Cl,ir (4,13,14) increases at low pH o and on cell swelling, but it inwardly rectifies. I Cl,Ca (9,11,24) requires an elevation of [Ca 2ϩ ] i for its activation.…”

Section: Discussionmentioning

confidence: 94%

Acidic extracellular pH-activated outwardly rectifying chloride current in mammalian cardiac myocytes

Yamamoto

Ehara²

2006

American Journal of Physiology-Heart and Circulatory Physiology

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Yamamoto, Shintaro, and Tsuguhisa Ehara. Acidic extracellular pH-activated outwardly rectifying chloride current in mammalian cardiac myocytes. Am J Physiol Heart Circ Physiol 290: H1905-H1914, 2006. First published December 9, 2005 doi:10.1152/ajpheart.00965.2005.-Extracellular acidic pH was found to induce an outwardly rectifying Cl Ϫ current (ICl,acid) in mouse ventricular cells, with a half-maximal activation at pH 5.9. The current showed the permeability sequence for anions to be SCN Ϫ Ͼ Br Ϫ Ͼ I Ϫ Ͼ Cl Ϫ Ͼ F Ϫ Ͼ aspartate, while it exhibited a time-dependent activation at large positive potentials. Similar currents were also observed in mouse atrial cells and in atrial and ventricular cells from guinea pig. Some Cl Ϫ channel blockers (DIDS, niflumic acid, and glibenclamide) inhibited I Cl,acid, whereas tamoxifen had little effect on it. Unlike volume-regulated Cl Ϫ current (I Cl,vol) and CFTR Cl Ϫ current (ICl,CFTR), ICl,acid was independent of the presence of intracellular ATP. Activation of I Cl,acid appeared to be also independent of intracellular Ca 2ϩ and G protein. ICl,acid and I Cl,vol could develop in an additive fashion in acidic hypotonic solutions. Isoprenaline-induced I Cl,CFTR was inhibited by acidification in a pH-dependent manner in guinea pig ventricular cells. Our results support the view that I Cl,acid and ICl,vol stem from two distinct populations of anion channels and that the I Cl,acid channels are present in cardiac cells. I Cl,acid may play a role in the control of action potential duration or cell volume under pathological conditions, such as ischemia-related cardiac acidosis. acidosis; chloride channel; heart CHLORIDE (Cl Ϫ ) channels play a role in a variety of cell functions, such as cell cycle, apoptosis, ion homeostasis, cell volume regulation, and muscle tone (for review see Refs. 11,12,and 20). Several types of Cl Ϫ currents have been recorded in native cardiac cells (for review see Refs. 9 and 11). These include Cl Ϫ currents activated by intracellular PKA (I Cl,PKA ), PKC (I Cl,PKC ), Ca 2ϩ (I Cl,Ca ), extracellular ATP (I Cl,ATP ), or cell swelling (I Cl,vol ) and an inwardly rectifying Cl Ϫ current (I Cl,ir ). The channels responsible for I Cl,PKA , I Cl,PKC , and I Cl,ATP likely share the same molecular basis derived from CFTR gene, and thus these currents can be unified as I Cl,CFTR (11). It has been shown that some of these Cl Ϫ currents depend on extracellular pH (pH o ). Acidic pH o enhances I Cl,Ca in rabbit ventricular cells (10) and I Cl,ir in rat atrial and ventricular cells (13,14) and inhibits I Cl,CFTR in guinea pig ventricular cells (17). The roles of such pH o -dependent attenuation of Cl Ϫ currents in cardiac electrical activity under pathophysiological conditions have been investigated (9 -11, 13, 14).On the other hand, a more directly pH o -dependent regulation has been found in cultured cells. Auzanneau et al. (1) Recently, however, Lambert and Oberwinkler (15) extensively studied the properties of I Cl,acid and I Cl,vol in HEK293 cells. Their import...

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Section: Discussionmentioning

confidence: 94%

Acidic extracellular pH-activated outwardly rectifying chloride current in mammalian cardiac myocytes

Yamamoto

Ehara²

2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Ϫ current (I Cl,ir ) has recently been described in cardiac myocytes (10). This current is sensitive to Cd 2ϩ and resistant to DIDS, which, with its inward rectification, distinguishes it from Cl Ϫ currents previously described in the heart.…”

Section: Effect Of Acidosis On I Cl In Ventricular Cells a Novel Inwmentioning

confidence: 91%

Electrophysiological response of rat ventricular myocytes to acidosis

Komukai

Brette

Pascarel

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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The effects of acidosis on the action potential, resting potential, L-type Ca2+( I Ca), inward rectifier potassium ( I K1), delayed rectifier potassium ( I K), steady-state ( I SS), and inwardly rectifying chloride ( I Cl,ir) currents of rat subepicardial (Epi) and subendocardial (Endo) ventricular myocytes were investigated using the patch-clamp technique. Action potential duration was shorter in Epi than in Endo cells. Acidosis (extracellular pH decreased from 7.4 to 6.5) depolarized the resting membrane potential and prolonged the time for 50% repolarization of the action potential in Epi and Endo cells, although the prolongation was larger in Endo cells. At control pH, I Ca, I K1, and I SS were not significantly different in Epi and Endo cells, but I K was larger in Epi cells. Acidosis did not alter I Ca, I K1, or I K but decreased I SS; this decrease was larger in Endo cells. It is suggested that the acidosis-induced decrease in I SS underlies the prolongation of the action potential. I Cl,ir at control pH was Cd2+ sensitive but 4,4′-disothiocyanato-stilbene-2,2′-disulfonic acid resistant. Acidosis increased I Cl,ir; it is suggested that the acidosis-induced increase in I Cl,ir underlies the depolarization of the resting membrane potential.

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“…Jentsch et al, 2002;Clark et al, 1998;Duan et al, 2000), both the muscular and the photoreceptor Cl -currents (Ugarte et al, 2005) were blocked by 9-AC with moderate efficiency. Block by extracellularly applied Zn 2+ or Cd 2+ was not observed in the current study.…”

Section: Basic Characteristics Of Dmclc-2 Currents In Drosophila Musclementioning

confidence: 94%

“…Clark et al, 1998;Gründer et al, 1992;Duan et al, 2000;Rutledge et al, 2001) and represents one of the characteristics of ClC-2 currents. The present work showed a considerable augmentation of I Cl,H that might be relevant for regulatory volume decrease as supported by experiments on insect cells (Xiong et al, 1999) and Xenopus oocytes (Furukawa et al, 1998).…”

Section: Basic Characteristics Of Dmclc-2 Currents In Drosophila Musclementioning

confidence: 99%

Properties and possible function of a hyperpolarisation-activated chloride current in Drosophila

Rose

Derst

Wanischeck

et al. 2007

Journal of Experimental Biology

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SUMMARY A chloride current, ICl,H, slowly activating on hyperpolarisation was investigated in Drosophila melanogaster larval muscles using the two-electrode voltage clamp. Sizeable currents were observed after the intracellular chloride concentration([Cl–]i) had been elevated by diffusion of Cl– from the electrodes. The time course of ICl,H was rather variable and required two exponentials to be accurately described. The reversal potential, –40 to –20 mV in Cl–-loaded fires, shifted on lowering external[Cl–] in the positive direction. Steady-state activation of ICl,H was characterised by V0.5 of≈–120 mV and a slope factor, k, of ≈10 mV at a[Cl–]i ≈35 mmol l–1. Raising[Cl–]i to ≈50 mmol l–1 caused a negative shift of V0.5 equivalent to the change of ECl and led to a nearly threefold increase in maximal steady-state conductance. ICl,H was resistant to 10 mmol l–1 Zn2+ and 1 mmol l–1Cd2+ but was greatly reduced by 1 mmol l–19-anthracenecarboxylic acid (9-AC). ICl,H was affected by changes of extracellular pH and increased on lowering extracellular osmolality. 9-AC also decreased muscle fibre resting conductance by approximately 20% and increased muscle contractions. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis confirmed the expression of all three ClC genes in muscle, and immunohistochemistry indicated location of Drosophila melanogaster chloride channel-2(DmClC-2) at the Z-lines. We conclude that DmClC-2 accounts for the channels underlying ICl,H, and in part for the resting chloride conductance. DmClC-2 may serve general homeostatic mechanisms such as pH- and osmo-regulation or may support muscle function on high motor activity or during a particular neurohormonal state of the animal.

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A Novel Anionic Inward Rectifier in Native Cardiac Myocytes

Cited by 68 publications

References 70 publications

Acidic extracellular pH-activated outwardly rectifying chloride current in mammalian cardiac myocytes

Acidic extracellular pH-activated outwardly rectifying chloride current in mammalian cardiac myocytes

Electrophysiological response of rat ventricular myocytes to acidosis

Properties and possible function of a hyperpolarisation-activated chloride current in Drosophila

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