Depletion of T-tubules and specific subcellular changes in sarcolemmal proteins in tachycardia-induced heart failure

Balijepalli, Ravi C.; Lokuta, Andrew J.; Maertz, Nathan A.; Buck, Jennifer M.; Haworth, Robert A.; Valdivia, Héctor H.; Kamp, Timothy J.

doi:10.1016/s0008-6363(03)00325-0

Cited by 159 publications

(138 citation statements)

References 34 publications

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“…Cardiac membrane fractions of WT and SUR2 mutant mouse heart tissues were prepared as previously described [25]. Tissues from 8 mice were pooled for isolation.…”

Section: Isolation Of Cardiac Membrane Fractions From Wt and The Sur2mentioning

confidence: 99%

“…A cardiac membrane fraction from WT mouse hearts was fractionated as previously described [25] and proteins isolated from the very top fraction showed no detectable mitochondrial contamination in gels based on a Western blot analysis (Fig. 6A, left panel) of two mitochondria markers, VDAC1 (outer membrane) and COXIV (inner membrane), while a plasma membrane marker, Na/K ATPase was abundantly present.…”

Section: Identification Of Constituents That Confer I Katpnmentioning

confidence: 99%

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Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity

Pu¹,

Ye²,

Kroboth³

et al. 2008

Journal of Molecular and Cellular Cardiology

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The cardiac sarcolemmal ATP-sensitive potassium channel (K ATP ) consists of a Kir6.2 pore and a SUR2 regulatory subunit, which is an ATP-binding cassette (ABC) transporter. K ATP channels have been proposed to play protective roles during ischemic preconditioning. A SUR2 mutant mouse was previously generated by disrupting the first nucleotide-binding domain (NBD1), where a glibenclamide action site was located. In the mutant ventricular myocytes, a non-conventional glibenclamide-insensitive (10 μM), ATP-sensitive current (I KATPn ) was detected in 33% of singlechannel recordings with an average amplitude of 12.3±5.4 pA per patch, an IC 50 to ATP inhibition at 10 μM, and a mean burst duration at 20.6±1.8 ms. Newly designed SUR2-isoform or variantspecific antibodies identified novel SUR2 short forms in the sizes of 28 and 68 kDa in addition to a 150-kDa long form in the sarcolemmal membrane of wild-type (WT) heart. We hypothesized that channels constituted by these short forms that lack NBD1, confer I KATPn . The absence of the long form in the mutant corresponded to loss of the conventional glibenclamide-sensitive K ATP currents (I KATP ) in isolated cardiomyocytes and vascular smooth muscle cells but the SUR2 short forms remained intact. Nested exonic RT-PCR in the mutant indicated that the short forms lacked NBD1 but contained NBD2. The SUR2 short forms co-immunoprecipitated with Kir6.1 or Kir6.2 suggesting that the short forms may function as hemi-transporters reported in other eukaryotic ABC transporter subgroups. Our results indicate that different K ATP compositions may co-exist in cardiac sarcolemmal membrane.

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“…Cardiac membrane fractions of WT and SUR2 mutant mouse heart tissues were prepared as previously described [25]. Tissues from 8 mice were pooled for isolation.…”

Section: Isolation Of Cardiac Membrane Fractions From Wt and The Sur2mentioning

confidence: 99%

Section: Identification Of Constituents That Confer I Katpnmentioning

confidence: 99%

Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity

Pu¹,

Ye²,

Kroboth³

et al. 2008

Journal of Molecular and Cellular Cardiology

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“…These findings, in combination with diffusional limitations in TATS's lumen (3,8), raise the possibility that AP may differ among membrane domains. Further interest in the TATS AP stems from the recent finding of loss and disorganization of tubules in several pathological conditions, including heart failure (9)(10)(11)(12)(13)(14). Because correlation between morphological TATS alterations and Ca 2+ -release asynchronicity has been observed (14,15), recording AP propagation in TATS can elucidate the fundamental electrophysiological mechanism linking structural and functional anomalies.…”

mentioning

confidence: 99%

Action potential propagation in transverse-axial tubular system is impaired in heart failure

Sacconi

Ferrantini

Lotti

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

123

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The plasma membrane of cardiac myocytes presents complex invaginations known as the transverse-axial tubular system (TATS). Despite TATS's crucial role in excitation-contraction coupling and morphological alterations found in pathological settings, TATS's electrical activity has never been directly investigated in remodeled tubular networks. Here we develop an ultrafast random access multiphoton microscope that, in combination with a customly synthesized voltage-sensitive dye, is used to simultaneously measure action potentials (APs) at multiple sites within the sarcolemma with submillisecond temporal and submicrometer spatial resolution in real time. We find that the tight electrical coupling between different sarcolemmal domains is guaranteed only within an intact tubular system. In fact, acute detachment by osmotic shock of most tubules from the surface sarcolemma prevents AP propagation not only in the disconnected tubules, but also in some of the tubules that remain connected with the surface. This indicates that a structural disorganization of the tubular system worsens the electrical coupling between the TATS and the surface. The pathological implications of this finding are investigated in failing hearts. We find that AP propagation into the pathologically remodeled TATS frequently fails and may be followed by local spontaneous electrical activity. Our findings provide insight on the relationship between abnormal TATS and asynchronous calcium release, a major determinant of cardiac contractile dysfunction and arrhythmias.cardiac disease | nonlinear microscopy | voltage imaging | t tubules T he transverse-axial tubular system (TATS) is a complex network characterized by transverse (t tubules, TT) and longitudinal (axial tubules, AT) components running from one transverse tubule to the next (1-3). The TATS of a myocyte rapidly conducts depolarization of the surface sarcolemma (SS) to the core of the cardiomyocyte (4). The coupling between sarcolemmal Ca 2+ entry during an action potential (AP) and Ca 2+ release from sarcoplasmic reticulum (SR) promotes synchronous myofibril activation throughout the myocyte (5). Recent studies highlight that AP-relevant ion channels and transporters are expressed in TATS membrane with different densities and isoforms from those in SS (6, 7). These findings, in combination with diffusional limitations in TATS's lumen (3,8), raise the possibility that AP may differ among membrane domains. Further interest in the TATS AP stems from the recent finding of loss and disorganization of tubules in several pathological conditions, including heart failure (9-14). Because correlation between morphological TATS alterations and Ca 2+ -release asynchronicity has been observed (14, 15), recording AP propagation in TATS can elucidate the fundamental electrophysiological mechanism linking structural and functional anomalies.Although the uniformity of the AP across the whole sarcolemma has been mathematically (16) and experimentally (17) proved, a potential alteration of the AP propagation i...

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“…Depletion of T-tubules occurs in failing ventricular myocytes with rapid pacing, with associated decreases in the density of L-type calcium channels and beta-adrenergic receptors in both surface and T-tubular sarcolemmata. This heterogeneous loss of T-tubules results in abnormal excitation-contraction coupling and may impair contractile efficiency by causing variability in time course of activation of cells (10).…”

Section: Pathophysiology and Proposed Mechanisms Systolic Functionmentioning

confidence: 99%

Tachycardia mediated cardiomyopathy: Pathophysiology, mechanisms, clinical features and management

Gupta¹,

Figueredo²

2014

International Journal of Cardiology

108

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Depletion of T-tubules and specific subcellular changes in sarcolemmal proteins in tachycardia-induced heart failure

Cited by 159 publications

References 34 publications

Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity

Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity

Action potential propagation in transverse-axial tubular system is impaired in heart failure

Tachycardia mediated cardiomyopathy: Pathophysiology, mechanisms, clinical features and management

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