Swelling-Activated Chloride Current Is Persistently Activated in Ventricular Myocytes From Dogs With Tachycardia-Induced Congestive Heart Failure

Clemo, Henry F.; Stambler, Bruce S.; Baumgarten, Clive M.

doi:10.1161/01.res.84.2.157

Cited by 92 publications

(77 citation statements)

References 53 publications

(72 reference statements)

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“…2Ca). This property is similar to basal activation of VRAC current in cells from the canine CHF model (32). Interestingly, the basal activation of VRAC current in cells from 8-week TAC mice was smaller than that from 4-week TAC mice, and the hypotonic solution induced a VRAC current (difference current) that was also smaller than that from sham-operated mice (Fig.…”

Section: Vrac In Cardiac Hypertrophysupporting

confidence: 70%

“…Baumgarten and co-workers identified that this is Cl − current passing through VRAC. They found that the sarcolemmal surface area (an index of cell volume) is larger, as evidenced by an approximately 20% increase in membrane capacitance (another index of cell volume) in ventricular myocytes from a pacing-induced congestive heart failure (CHF) canine model and showed that the basally activated Cl − current in the CHF cells exhibits similar properties to VRAC (32). Moreover, they showed preliminary data that a tamoxifen-sensitive VRAC was also persistently activated in human atrial myocytes obtained from patients with right atrial enlargement and/or elevated left ventricular end-diastolic pressure (33).…”

Section: Vrac In Cardiac Hypertrophymentioning

confidence: 99%

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New Molecular Mechanisms for Cardiovascular Disease: Cardiac Hypertrophy and Cell-Volume Regulation

et al. 2011

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Abstract. Cardiac hypertrophy is an increase in the muscle volume of the ventricle due to the enlargement of cardiac cells. Physiological cardiac hypertrophy is the normal response to healthy exercise, and pathological hypertrophy is the response to increased stress such as hypertension. Intracellular and extracellular aniosmotic conditions also change cell volume. Since persistent cell swelling or cell shrinkage during aniosmotic conditions results in cell death, the ability to regulate cell volume is important for the maintenance of cellular homeostasis. Cell swelling activates a regulatory volume decrease (RVD) response in which solute leakage pathways are stimulated and solute with water exits cells, reducing the cell volume towards the original value. In cardiac cells, one of the essential factors for cell-volume regulation is the volume-regulated anion channel (VRAC). However, the relationship between cardiac hypertrophy and cell-volume regulation is not clear. In this review, we introduce our recent findings showing that the impairment of VRAC current is exhibited in ventricular cells from mice with cardiac hypertrophy induced by transverse aortic constriction. Similar results were shown in caveolin-3-deficient mice, which develop cardiac hypertrophy without pressure overload. These results suggest that VRAC will be a new target for protection from the development of cardiac hypertrophy.

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Section: Vrac In Cardiac Hypertrophysupporting

confidence: 70%

Section: Vrac In Cardiac Hypertrophymentioning

confidence: 99%

New Molecular Mechanisms for Cardiovascular Disease: Cardiac Hypertrophy and Cell-Volume Regulation

et al. 2011

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“…4). The eventual reduction in APD is likely to be due to the slow activation of swelling-activated currents including I Cl,swell (8,11,33) and the slow delayed rectifying K current (I Ks ) (29,44), as well as the depression of I Ca-L shown here and by others (4).…”

Section: Discussionsupporting

confidence: 50%

“…To evaluate this possibility, myocytes were osmotically swollen for 20 min in 0.6T solution and then returned to 1T solution for 10 min. Figure 3 displays recordings of the action potential and cell shortening in a representative myocyte before and at selected times (1,5,8, and 20 min) after a hyposmotic challenge in 0.6T solution. Whereas almost all of the depolarization of resting E m occurred over 2-3 min, APD continued to decrease throughout the 20-min exposure to 0.6T (Fig.…”

Section: Effect Of Brief Osmotic Swelling On Cell Shorteningmentioning

confidence: 99%

Biphasic effects of cell volume on excitation-contraction coupling in rabbit ventricular myocytes

Zhang

Satin

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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.-We studied the effects of osmotic swelling on the components of excitation-contraction coupling in ventricular myocytes. Myocyte volume rapidly increased 30% in hyposmotic (0.6T) solution and was constant thereafter. Cell shortening transiently increased 31% after 4 min in 0.6T but then decreased to 68% of control after 20 min. In parallel, the L-type Ca 2ϩ current (ICa-L) transiently increased 10% and then declined to 70% of control. Similar biphasic effects on shortening were observed under current clamp. In contrast, action potential duration was unchanged at 4 min but decreased to 72% of control after 20 min. Ca 2ϩ transients were measured with fura 2-AM. The emission ratio with excitation at 340 and 380 nm (f 340/f380) decreased by 12% after 3 min in 0.6T, whereas shortening and I Ca-L increased at the same time. After 8 min, shortening, I Ca-L, and the f340/f380 ratio decreased 28, 25, and 59%, respectively. The results suggest that osmotic swelling causes biphasic changes in I Ca-L that contribute to its biphasic effects on contraction. In addition, swelling initially appears to reduce the Ca 2ϩ transient initiated by a given ICa-L, and later, both I Ca-L and the Ca 2ϩ transient are inhibited.osmolarity; action potential duration; calcium current; calcium transient; cell shortening SWELLING OF CARDIAC MYOCYTES is a prominent aspect of the response to ischemia-reperfusion and elective cardioplegia and also may arise in renal insufficiency and syndromes with inappropriate secretion of antidiuretic hormone. Altered myocyte hydration has important functional consequences. Osmotic perturbations modulate both electrical activity (for reviews, see 34,38,42) and the ability of cardiac muscle to contract (5,16,17). Although facets of the contractile response to osmotic swelling are known from studies on multicellular preparations, little mechanistic information is available at the single cell level to explain the implications of myocyte swelling for excitation-contraction (E-C) coupling. Moreover, the effect of swelling on L-type Ca 2ϩ current (I Ca-L ), a critical aspect of E-C coupling, remains controversial. Under ruptured patch voltage-clamp conditions, for example, swelling is reported to enhance I Ca-L in rabbit atrial and sinoatrial node cells (22), depress I Ca-L in rat ventricular cells (4), and to have no significant effect in guinea pig (13, 31) and canine (44) ventricular cells. A swelling-induced enhancement of I Ca-L also has been claimed based on fura 2 measurements of diltiazem-sensitive Ca 2ϩ influx (36). It is unclear whether these differences in the response of I Ca-L to myocyte swelling arise from species differences or from methodological issues, such as the composition of the patch pipette solution, the effectiveness of cell dialysis, or the variable extent of myocyte swelling under ruptured-patch conditions (6, 33). Several other species differences in E-C coupling, including the sensitivity of contraction to inhibition of the sarcoplasmic reticulum (SR), are well known (2).The present stu...

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“…14,15 Activation of I Cl,swell causes resting membrane depolarization and APD shortening, 14,15,18,19 and persistent I Cl,swell activation has been described in isolated canine ventricular myocytes after rapid pacing. 20 The reversal potential (E Cl ) of I Cl,swell is Ϫ30 to Ϫ40 mV; thus, inward or outward currents may be generated depending on the membrane potential. On average, the membrane potential during AF is more depolarized (positive to E Cl ) relative to sinus rhythm because of rapid repetitive stimulation.…”

Section: Akar Et Al Pacing-induced Intracellular Chloride Accumulationmentioning

confidence: 99%

Intracellular Chloride Accumulation and Subcellular Elemental Distribution During Atrial Fibrillation

Akar

Everett

et al. 2003

Circulation

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Background-Ion channel remodeling occurs during atrial fibrillation (AF); however, the extent of alteration in the subcellular distribution of elements (Na, K, Cl, Ca, Mg, P) is unknown. Electron probe microanalysis was used to determine the total (freeϩbound) in vivo subcellular concentration of these elements during AF. Methods and Results-The left atrial appendage (LAA) was snap-frozen in situ after pacing (640 bpm) for 3 minutes (nϭ5 dogs), 30 minutes (nϭ3), or 48 hours (nϭ5). Dogs in sinus rhythm (nϭ3) served as controls. Whole-cell, cytosolic, and mitochondrial elemental concentrations were measured in cryosections. LAA effective refractory period (ERP) was measured before and after pacing. LAA ERP decreased significantly after 48 hours (116Ϯ3 to 88Ϯ10 ms, Pϭ0.02).Whole-cell Cl increased by 9.0 mmol/L and 17 mmol/L after 3 and 30 minutes of pacing, respectively (PϽ0.0001), without a concomitant increase in Na. However, at 48 hours, whole-cell Na was reduced by 51% (PϽ0.01). Cytosolic Ca increased by 1.1 mmol/kg dry wt after 3 minutes (PϽ0.005), but mitochondrial Ca remained low and unchanged. Cell size measured in transverse cryosections increased after 3 minutes of pacing (75Ϯ5 to 109Ϯ11 m 2 , Pϭ0.007) but returned to baseline by 30 minutes (66Ϯ5 m 2 ). Conclusions-IntracellularCl accumulation induced by rapid pacing is a novel finding and may play a role in AF pathogenesis by causing resting membrane depolarization and ERP reduction. There was no evidence of cellular or mitochondrial Ca overload despite the development of electrical remodeling and transient increase in cytoplasmic Ca.

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Swelling-Activated Chloride Current Is Persistently Activated in Ventricular Myocytes From Dogs With Tachycardia-Induced Congestive Heart Failure

Cited by 92 publications

References 53 publications

New Molecular Mechanisms for Cardiovascular Disease: Cardiac Hypertrophy and Cell-Volume Regulation

New Molecular Mechanisms for Cardiovascular Disease: Cardiac Hypertrophy and Cell-Volume Regulation

Biphasic effects of cell volume on excitation-contraction coupling in rabbit ventricular myocytes

Intracellular Chloride Accumulation and Subcellular Elemental Distribution During Atrial Fibrillation

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