Autonomic Regulation of Voltage‐Gated Cardiac Ion Channels

Shibata, Erwin F.; Brown, Tracy L.; Washburn, Zachary W.; Bai, Jing; Revak, Thomas J.; Butters, Carol A.

doi:10.1111/j.1540-8167.2006.00387.x

Cited by 48 publications

(60 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previously shown (15,28) and confirmed in this study, 10 mol/l ISO (a ␤-AR agonist) increased the peak I Na density by 36% (from 61.2 Ϯ 7.1 to 83.2 Ϯ 5.3 pA/pF, n ϭ 15, P Ͻ 0.05). The involvement of G s ␣ and Cav-3 is illustrated by the family of current traces in Fig.…”

Section: Resultssupporting

confidence: 70%

“…Caveolae are cholesterol-and sphingolipid-enriched plasma membrane invaginations containing a signature scaffolding integral membrane protein called caveolin (24). Caveolae are immobile vesicles (31) whose neck opening is regulated in a dynamic fashion, and this is known to modulate the continuity between the intracaveolar and extracellular spaces (28). However, the mechanism(s) responsible for this regulation has not been clearly defined.…”

mentioning

confidence: 99%

“…Recent studies have identified both cardiac sodium channels (Na v 1.5) (27,28,33) and L-type calcium channels [voltagegated calcium channel subunit 1.2a (Ca v 1.2a)] (2,16,28) in cardiomyocyte cellular reservoirs-caveolae. Caveolae are cholesterol-and sphingolipid-enriched plasma membrane invaginations containing a signature scaffolding integral membrane protein called caveolin (24).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Regulation of caveolar cardiac sodium current by a single G_sα histidine residue

Palygin¹,

Pettus²,

Shibata³

2008

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

Palygin OA, Pettus JM, Shibata EF. Regulation of caveolar cardiac sodium current by a single Gs␣ histidine residue. Am J Physiol Heart Circ Physiol 294: H1693-H1699, 2008. First published February 8, 2008 doi:10.1152/ajpheart.01337.2007.-Cardiac sodium channels (voltage-gated Na ϩ channel subunit 1.5) reside in both the plasmalemma and membrane invaginations called caveolae. Opening of the caveolar neck permits resident channels to become functional. In cardiac myocytes, caveolar opening can be stimulated by applying ␤-receptor agonists, which initiates an interaction between the stimulatory G protein subunit-␣ (Gs␣) and caveolin-3. This study shows that, in adult rat ventricular myocytes, a functional Gs␣-caveolin-3 interaction occurs, even in the absence of the caveolin-binding sequence motif of Gs␣. Consistent with previous data, whole cell experiments conducted in the presence of intracellular PKA inhibitor stimulation with ␤-receptor agonists increased the sodium current (INa) by 35.9 Ϯ 8.6% (P Ͻ 0.05), and this increase was mimicked by application of Gs␣ protein. Inclusion of anti-caveolin-3 antibody abolished this effect. These findings suggest that Gs␣ and caveolin-3 are components of a PKA-independent pathway that leads to the enhancement of INa. In this study, alanine scanning mutagenesis of Gs␣ (40THR42), in conjunction with voltage-clamp studies, demonstrated that the histidine residue at position 41 of Gs␣ (H41) is a critical residue for the functional increase of INa. Protein interaction assays suggest that Gs␣FL (full length) binds to caveolin-3, but the enhancement of INa is observed only in the presence of Gs␣ H41. We conclude that Gs␣ H41 is a critical residue in the regulation of the increase in INa in ventricular myocytes.

show abstract

Section: Resultssupporting

confidence: 70%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Regulation of caveolar cardiac sodium current by a single G_sα histidine residue

Palygin¹,

Pettus²,

Shibata³

2008

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, to date, the site of interaction between CAV3 and Na v 1.5 is still unknown. Immunohistostaining experiments using cardiac tissues clearly demonstrate that the two proteins are colocalized (398,439,464). Dystrophin has also been shown to be a component of caveolae (105), raising the possibility that the interaction of CAV3 with Na v 1.5 could be indirect, via proteins of the DGC (138).…”

Section: Caveolinsmentioning

confidence: 99%

Dynamic of Ion Channel Expression at the Plasma Membrane of Cardiomyocytes

Balse

Steele

Abriel

et al. 2012

Physiological Reviews

106

View full text Add to dashboard Cite

Cardiac myocytes are characterized by distinct structural and functional entities involved in the generation and transmission of the action potential and the excitation-contraction coupling process. Key to their function is the specific organization of ion channels and transporters to and within distinct membrane domains, which supports the anisotropic propagation of the depolarization wave. This review addresses the current knowledge on the molecular actors regulating the distinct trafficking and targeting mechanisms of ion channels in the highly polarized cardiac myocyte. In addition to ubiquitous mechanisms shared by other excitable cells, cardiac myocytes show unique specialization, illustrated by the molecular organization of myocyte-myocyte contacts, e.g., the intercalated disc and the gap junction. Many factors contribute to the specialization of the cardiac sarcolemma and the functional expression of cardiac ion channels, including various anchoring proteins, motors, small GTPases, membrane lipids, and cholesterol. The discovery of genetic defects in some of these actors, leading to complex cardiac disorders, emphasizes the importance of trafficking and targeting of ion channels to cardiac function. A major challenge in the field is to understand how these and other actors work together in intact myocytes to fine-tune ion channel expression and control cardiac excitability.

show abstract

“…These include aquaporin water channels (1-3), CFTR (4), N-type Ca 2ϩ channels (5), NHE3 (6), cardiac Na ϩ channels (7,8), and a broad range of voltage-gated, inwardly rectified and Ca 2ϩ -activated potassium channels (reviewed in Ref. 9,10).…”

mentioning

confidence: 99%

The Epithelial Sodium Channel (ENaC) Traffics to Apical Membrane in Lipid Rafts in Mouse Cortical Collecting Duct Cells

Hill

Butterworth

Wang

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

We previously showed that ENaC is present in lipid rafts in A6 cells, a Xenopus kidney cell line. We now demonstrate that ENaC can be detected in lipid rafts in mouse cortical collecting duct ( MPK CCD 14 ) cells by detergent insolubility, buoyancy on density gradients using two distinct approaches, and colocalization with caveolin 1. Less than 30% of ENaC subunits were found in raft fractions. The channel subunits also colocalized on sucrose gradients with known vesicle targeting and fusion proteins syntaxin 1A, Vamp 2, and SNAP23. Hormonal stimulation of ENaC activity by either forskolin or aldosterone, short or long term, did not alter the lipid raft distribution of ENaC. Methyl-␤-cyclodextrin added apically to MPK CCD 14 cells resulted in a slow decline in amiloride-sensitive sodium transport with short circuit current reductions of 38.1 ؎ 9.6% after 60 min. The slow decline in ENaC activity in response to apical cyclodextrin was identical to the rate of decline seen when protein synthesis was inhibited by cycloheximide. Apical biotinylation of MPK CCD 14 cells confirmed the loss of ENaC at the cell surface following cyclodextrin treatment. Acute stimulation of the recycling pool of ENaC was unaffected by apical cyclodextrin application. Expression of dominant negative caveolin isoforms (CAV1-eGFP and CAV3-DGV) which disrupt caveolae, reduced basal ENaC currents by 72.3 and 78.2%, respectively; but, as with cyclodextrin, the acute response to forskolin was unaffected. We conclude that ENaC is present in and regulated by lipid rafts. The data are consistent with a model in which rafts mediate the constitutive apical delivery of ENaC.

show abstract

Autonomic Regulation of Voltage‐Gated Cardiac Ion Channels

Cited by 48 publications

References 49 publications

Regulation of caveolar cardiac sodium current by a single G_sα histidine residue

Regulation of caveolar cardiac sodium current by a single G_sα histidine residue

Dynamic of Ion Channel Expression at the Plasma Membrane of Cardiomyocytes

The Epithelial Sodium Channel (ENaC) Traffics to Apical Membrane in Lipid Rafts in Mouse Cortical Collecting Duct Cells

Contact Info

Product

Resources

About

Autonomic Regulation of Voltage‐Gated Cardiac Ion Channels

Cited by 48 publications

References 49 publications

Regulation of caveolar cardiac sodium current by a single Gsα histidine residue

Regulation of caveolar cardiac sodium current by a single Gsα histidine residue

Dynamic of Ion Channel Expression at the Plasma Membrane of Cardiomyocytes

The Epithelial Sodium Channel (ENaC) Traffics to Apical Membrane in Lipid Rafts in Mouse Cortical Collecting Duct Cells

Contact Info

Product

Resources

About

Regulation of caveolar cardiac sodium current by a single G_sα histidine residue

Regulation of caveolar cardiac sodium current by a single G_sα histidine residue