In situ co-distribution and functional interactions of SAP97 with sinoatrial isoforms of HCN channels

Peters, Christian J.; Chow, Sarah S.; Angoli, Damiano; Nazzari, Hamed; Cayabyab, Francisco S.; Morshedian, Ala; Accili, Eric A.

doi:10.1016/j.yjmcc.2009.01.010

Cited by 23 publications

(18 citation statements)

References 49 publications

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“…SAP97 is expressed both in atrial and ventricular myocytes. Immunofluorescence studies performed in myocardial sections show that SAP97 is predominantly localized at the extremity of myocytes at or near the ID, but some staining can also be seen laterally along the plasma membrane (110,146,232,294,328,330). One study found that SAP97 is localized also to the t-tubule system in isolated ventricular myocytes (232).…”

Section: Figurementioning

confidence: 99%

Dynamic of Ion Channel Expression at the Plasma Membrane of Cardiomyocytes

Balse

Steele

Abriel

et al. 2012

Physiological Reviews

107

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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.

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Section: Figurementioning

confidence: 99%

Dynamic of Ion Channel Expression at the Plasma Membrane of Cardiomyocytes

Balse

Steele

Abriel

et al. 2012

Physiological Reviews

107

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“…HCN channel properties have been shown to be altered by interaction 64 with caveolin-3 (cav-3), MiRP1, KCR1 and SAP97 proteins [10][11][12][13][14][15].…”

mentioning

confidence: 99%

A caveolin-binding domain in the HCN4 channels mediates functional interaction with caveolin proteins

Barbuti

Scavone

Mazzocchi

et al. 2012

Journal of Molecular and Cellular Cardiology

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Section: Discussionmentioning

confidence: 99%

“…Originally described in the brain at neuronal synapses (75), there is increasing evidence that these scaffolds play a similar role in the heart (1,7,27,39,45,46,53,61,63,81). It has been shown that interaction of cardiac ion channels with SAP97 occurs with a number of potassium channels including Kv1.5, Kv4, Kir2.2 and 2.3, and the hyperpolarization-activated, cyclic nucleotidegated channels (1,7,27,45,46,61,81). These ion channels interact with SAP97 through standard PDZ-domain binding to the terminal most amino acids of the ion channel (1,27,45,46,53,61,81) and appear to play an important role in regulation of channel density at the cardiac myocyte membranes (1,79).…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that interaction of cardiac ion channels with SAP97 occurs with a number of potassium channels including Kv1.5, Kv4, Kir2.2 and 2.3, and the hyperpolarization-activated, cyclic nucleotidegated channels (1,7,27,45,46,61,81). These ion channels interact with SAP97 through standard PDZ-domain binding to the terminal most amino acids of the ion channel (1,27,45,46,53,61,81) and appear to play an important role in regulation of channel density at the cardiac myocyte membranes (1,79). We show here direct interaction between Panx1 and SAP97, which is important for Panx1 channel density in the membrane.…”

Section: Discussionmentioning

confidence: 99%

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Cardiomyocyte ATP release through pannexin 1 aids in early fibroblast activation

Dolmatova

Spagnol

Boassa

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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HS. Cardiomyocyte ATP release through pannexin 1 aids in early fibroblast activation. Am J Physiol Heart Circ Physiol 303: H1208 -H1218, 2012. First published September 14, 2012; doi:10.1152/ajpheart.00251.2012.-Fibrosis following myocardial infarction is associated with increases in arrhythmias and sudden cardiac death. Initial steps in the development of fibrosis are not clear; however, it is likely that cardiac fibroblasts play an important role. In immune cells, ATP release from pannexin 1 (Panx1) channels acts as a paracrine signal initiating activation of innate immunity. ATP has been shown in noncardiac systems to initiate fibroblast activation. Therefore, we propose that ATP release through Panx1 channels and subsequent fibroblast activation in the heart drives the development of fibrosis in the heart following myocardial infarction. We identified for the first time that Panx1 is localized within sarcolemmal membranes of canine cardiac myocytes where it directly interacts with the postsynaptic density 95/Drosophila disk large/zonula occludens-1-containing scaffolding protein synapseassociated protein 97 via its carboxyl terminal domain (amino acids 300 -357). Induced ischemia rapidly increased glycosylation of Panx1, resulting in increased trafficking to the plasma membrane as well as increased interaction with synapse-associated protein 97. Cellular stress enhanced ATP release from myocyte Panx1 channels, which, in turn, causes fibroblast transformation to the activated myofibroblast phenotype via activation of the MAPK and p53 pathways, both of which are involved in the development of cardiac fibrosis. ATP release through Panx1 channels in cardiac myocytes during ischemia may be an early paracrine event leading to profibrotic responses to ischemic cardiac injury. fibrosis; paracrine signal; sudden cardiac death; ischemia IN CARDIAC INJURY, fibroblasts are activated, causing them to transdifferentiate into myofibroblasts, leading to profibrotic responses such as production of extracellular matrix proteins, collagen, and cytokines (8). With time, expansion of the extracellular matrix leads to separation of surviving myocyte bundles, forming a heterogeneous substrate that leads to slowed conduction which promotes life-threatening arrhythmias. In regions distant to the site of injury, fibroblasts activate and migrate to sites of injury and are highly responsive to cytokines and chemokines (64). While activated fibroblasts are known to produce and secrete many of the signals for myofibroblast formation and migration, thus causing a positive feedback loop of activation, little is known about the initial stimulus within the injured region that begins the activation process. It has been assumed that fibroblasts sense the environment and respond accordingly, but how and what they are sensing during very early stages of cardiac injury are unknown. Our studies suggest that ATP released from cardiac myocyte pannexin 1 (Panx1) channels initiates signaling in fibroblasts to begin the fibrotic process.Panx1 is ubiqui...

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In situ co-distribution and functional interactions of SAP97 with sinoatrial isoforms of HCN channels

Cited by 23 publications

References 49 publications

Dynamic of Ion Channel Expression at the Plasma Membrane of Cardiomyocytes

Dynamic of Ion Channel Expression at the Plasma Membrane of Cardiomyocytes

A caveolin-binding domain in the HCN4 channels mediates functional interaction with caveolin proteins

Cardiomyocyte ATP release through pannexin 1 aids in early fibroblast activation

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