Density and function of inward currents in right atrial cells from chronically fibrillating canine atria

Yagi, Takuya; Pu, Jielin; Chandra, Parag; Hara, Motoki; Danilo, Peter; Rosen, Michael R.; Boyden, Penelope A.

doi:10.1016/s0008-6363(02)00279-1

Cited by 45 publications

(26 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A very consistent observation in different species challenged with AF or tachypacing is a reduction in voltage-gated L-type Ca 2ϩ channels, while Ttype channels seem to be unaffected (485). Ca 2ϩ overload is potentially lethal, and the downregulation of L-type channels can be seen as a logical response serving to reduce Ca 2ϩ influx to the myocytes (48,49,77,462,472). The acute benefits of decreasing Ca 2ϩ overload via a reduction in L-type Ca 2ϩ channels is, however, jeopardized in the longer perspective.…”

Section: Atrial Remodelingmentioning

confidence: 92%

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Schmitt

Grunnet

Olesen

2014

Physiological Reviews

186

197

View full text Add to dashboard Cite

About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K+ channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K+ channels drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K+ channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure. The underlying posttranscriptional and posttranslational remodeling of the individual K+ channels changes their activity and significance relative to each other, and they must be viewed together to understand their role in keeping a stable heart rhythm, also under menacing conditions like attacks of reentry arrhythmia.

show abstract

Section: Atrial Remodelingmentioning

confidence: 92%

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Schmitt

Grunnet

Olesen

2014

Physiological Reviews

186

197

View full text Add to dashboard Cite

show abstract

“…Among TTX-insensitive subunits, the voltage dependence and kinetics of I Na,1 match those of the cardiac channel (Na V 1.5) better than those of the peripheral nervous system (PNS) channels, Na V 1.8 or Na V 1.9. V 1/2,inact ranges from Ϫ81 to Ϫ106 mV in cardiac channels (Fearon and Brown 2004;O'Leary 1998;Valdivia et al 2005;Yagi et al 2002), but from Ϫ34 to Ϫ55 mV in PNS channels (Cummins et al 1999;Renganathan et al 2002). Inactivation time constants at 0 mV were 200 s in I Na,1 (Fig.…”

Section: Na ϩ Channel Subunit Compositionmentioning

confidence: 94%

Developmental Changes in Two Voltage-Dependent Sodium Currents in Utricular Hair Cells

Wooltorton¹,

Gaboyard²,

Hurley³

et al. 2007

Journal of Neurophysiology

112

View full text Add to dashboard Cite

. Two kinds of sodium current (I Na ) have been separately reported in hair cells of the immature rodent utricle, a vestibular organ. We show that rat utricular hair cells express one or the other current depending on age (between postnatal days 0 and 22, P0 -P22), hair cell type (I, II, or immature), and epithelial zone (striola vs. extrastriola). The properties of these two currents, or a mix, can account for descriptions of I Na in hair cells from other reports. The patterns of Na channel expression during development suggest a role in establishing the distinct synapses of vestibular hair cells of different type and epithelial zone. All type I hair cells expressed I Na,1 , a TTX-insensitive current with a very negative voltage range of inactivation (midpoint: Ϫ94 mV). I Na,2 was TTX sensitive and had less negative voltage ranges of activation and inactivation (inactivation midpoint: Ϫ72 mV). I Na,1 dominated in the striola at all ages, but current density fell by two-thirds after the first postnatal week. I Na,2 was expressed by 60% of hair cells in the extrastriola in the first week, then disappeared. In the third week, all type I cells and about half of type II cells had I Na,1 ; the remaining cells lacked sodium current. I Na,1 is probably carried by Na V 1.5 subunits based on biophysical and pharmacological properties, mRNA expression, and immunoreactivity. Na V 1.5 was also localized to calyx endings on type I hair cells. Several TTX-sensitive subunits are candidates for I Na,2 .

show abstract

“…6,7 Alterations in ion channel function ("ionic remodeling") are believed to be important in the AF-promoting consequences of atrial tachycardia. 6 -8 Ionic changes that have been reported include decreased transient outward current (I to ), 9 -11 L-type Ca 2ϩ current (I Ca ) 9,11,12 and Na ϩ current (I Na ), 13,14 and increased inward rectifier K ϩ currents. 10,11,15 Bosch et al 11 reported that atrial myocytes from AF patients show increases in both the background inward rectifier current I K1 and the acetylcholineinduced component.…”

Section: Ionic Changes In At Remodelingmentioning

confidence: 99%

Kir3-Based Inward Rectifier Potassium Current

et al. 2006

View full text Add to dashboard Cite

Background-We previously characterized a novel K ϩ current (I KH ) with properties of constitutively active acetylcholinerelated current in dog atrium. I KH is sensitive to tertiapin-Q (IC 50 Ϸ10 nmol/L), a highly selective Kir3 current blocker. This study assessed the role of I KH in atrial tachycardia (AT)-remodeled canine left atrium (LA) with the use of tertiapin-Q as a probe. Methods and Results-Dogs were subjected to 7 to 13 days of AT (400 bpm). Coronary-perfused LA preparations were studied intact or subjected to cardiomyocyte isolation. I KH was recorded with patch-clamp methods. AT pacing increased time-dependent hyperpolarization-activated current (I KH ) at Ϫ110 mV from Ϫ1.8Ϯ0.3 (control) to Ϫ3.4Ϯ0.5 pA/pF (AT) and the 100-nmol/L tertiapin-sensitive component from Ϫ1.5Ϯ0.4 (control) to Ϫ3.3Ϯ0.6 pA/pF (AT). Prolonged atrial tachyarrhythmias could be induced with single extrastimuli in AT-remodeled, but not control, preparations, reflecting the atrial fibrillation-promoting effects of AT remodeling. In AT-remodeled preparations, tachyarrhythmia duration averaged 11.0Ϯ5.2 seconds, with a cycle length of 108Ϯ6 ms. Tertiapin-Q decreased tachyarrhythmia duration (to 0.6Ϯ0.1 second; PϽ0.001) and increased tachyarrhythmia cycle length (to 175Ϯ10 ms; PϽ0.001). Atrial action potential duration (APD) was increased 65Ϯ6% by tertiapin in AT-remodeled hearts versus 19Ϯ2% (PϽ0.001) in control. In 2 AT-remodeled preparations, tachyarrhythmia lasted uninterrupted for Ͼ20 minutes; tertiapin-Q slowed and then terminated arrhythmia in both. Tertiapin had no effect on left ventricular cardiomyocyte currents or APD. Conclusions-AT remodeling increases I KH , and a highly selective Kir3 current antagonist, tertiapin-Q, increases APD and suppresses atrial tachyarrhythmias in AT-remodeled preparations without affecting ventricular electrophysiology. Constitutive acetylcholine-related K ϩ current contributes to AT-remodeling effects in dogs and is a potentially interesting antiarrhythmic target.

show abstract

Density and function of inward currents in right atrial cells from chronically fibrillating canine atria

Cited by 45 publications

References 39 publications

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Developmental Changes in Two Voltage-Dependent Sodium Currents in Utricular Hair Cells

Kir3-Based Inward Rectifier Potassium Current

Contact Info

Product

Resources

About