Maxi-K channels localize to caveolae in human myometrium: a role for an actin-channel-caveolin complex in the regulation of myometrial smooth muscle K<sup>+</sup> current

Brainard, Adam M.; Miller, Andrea J.; Martens, Jeffrey R.; England, Sarah K.

doi:10.1152/ajpcell.00399.2004

Cited by 109 publications

(109 citation statements)

References 47 publications

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“…Two differentially distributed Slo1 to caveolin-1 populations were also apparent from sucrose density fractionation because Slo1 was detected in both light (carbonate-resistant) and heavy (carbonate-solubilized) membrane fractions, whereas caveolin-1 was mostly present in light fractions. A bimodal distribution of Slo1 to caveolin-1 according to their solubilization properties also exists in human myometrial tissues (13). Supporting a subpopulation of aortic Slo1 in caveolin-1-rich microdomains are the co-IP results showing a fraction (ϳ20%) of Slo1 tightly associated with caveolin-1, which coincides with the percentage (ϳ30%) of double-immunolabeled cells showing a high degree of proximity between Slo1 and caveolin-1 proteins.…”

Section: Association Of Slo1 Protein With Caveolin-1 In Native Aorticsupporting

confidence: 55%

“…Mechanism of hSlo1 and Caveolin-1 Association-Positive evidence for a functional correlation or association between Slo1 and caveolin-1 has been observed in other tissues (5,(13)(14)(15)26). Pull-down experiments using glutathione S-transferase-caveolin-1 protein, and lysates of HEK293T cells expressing hSlo1 indicate that these two proteins can associate; however, an indirect binding cannot be ruled out (14).…”

Section: Association Of Slo1 Protein With Caveolin-1 In Native Aorticmentioning

confidence: 99%

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Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

Alioua¹,

Lü²,

Kumar³

et al. 2008

Journal of Biological Chemistry

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The large conductance, voltage-and Ca 2؉ -activated potassium (MaxiK, BK) channel and caveolin-1 play important roles in regulating vascular contractility. Here, we hypothesized that the MaxiK ␣-subunit (Slo1) and caveolin-1 may interact with each other. Slo1 and caveolin-1 physiological association in native vascular tissue is strongly supported by (i) detergent-free purification of caveolin-1-rich domains demonstrating a pool of aortic Slo1 co-migrating with caveolin-1 to light density sucrose fractions, (ii) reverse co-immunoprecipitation, and (iii) double immunolabeling of freshly isolated myocytes revealing caveolin-1 and Slo1 proximity at the plasmalemma. In HEK293T cells, Slo1-caveolin-1 association was unaffected by the smooth muscle MaxiK ␤1-subunit. Sequence analysis revealed two potential caveolin-binding motifs along the Slo1 C terminus, one equivalent, 1007 YNMLCFGIY 1015 , and another mirror image, 537 YT-EYLSSAF 545 , to the consensus sequence, XXXX XX . Deletion of 1007 YNMLCFGIY 1015 caused ϳ80% loss of Slo1-caveolin-1 association while preserving channel normal folding and overall Slo1 and caveolin-1 intracellular distribution patterns. 537 YTEYLSSAF 545 deletion had an insignificant dissociative effect. Interestingly, caveolin-1 coexpression reduced Slo1 surface and functional expression near 70% without affecting channel voltage sensitivity, and deletion of 1007 YNMLCF-GIY 1015 motif obliterated channel surface expression. The results suggest 1007 YNMLCFGIY 1015 possible participation in Slo1 plasmalemmal targeting and demonstrate its role as a main mechanism for caveolin-1 association with Slo1 potentially serving a dual role: (i) maintaining channels in intracellular compartments downsizing their surface expression and/or (ii) serving as anchor of plasma membrane resident channels to caveolin-1-rich membranes. Because the caveolin-1 scaffolding domain is juxtamembrane, it is tempting to suggest that Slo1-caveolin-1 interaction facilitates the tethering of the Slo1 C-terminal end to the membrane.Large conductance, voltage-and Ca 2ϩ -activated potassium (MaxiK, BK) 4 channels play important roles in vascular, neuronal, and urinary functions. In vascular smooth muscle, MaxiK channel appears to be a unique signaling protein because of its ability to mediate the effects of several vasoconstricting as well as vasodilating agents. The ability of MaxiK protein to complete with high fidelity these opposite tasks calls for specific associations and subcellular compartmentalization with corresponding signaling partners (1). Recently, it has been appreciated that many signaling molecules are segregated primarily in specialized microdomains like caveolae (plasma membrane invaginations enriched with cholesterol and caveolin protein), thereby, optimizing signal transduction between agonists and specific effectors (2).Three caveolin proteins have been identified, caveolin-1, -2, and -3. All of them seem to be expressed in smooth muscle (3, 4). However, gene ablation experiments have shown that caveolin-1 p...

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Section: Association Of Slo1 Protein With Caveolin-1 In Native Aorticsupporting

confidence: 55%

Section: Association Of Slo1 Protein With Caveolin-1 In Native Aorticmentioning

confidence: 99%

Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

Alioua¹,

Lü²,

Kumar³

et al. 2008

Journal of Biological Chemistry

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“…Caveolae and their structural proteins CAVs (Okamoto et al 1998) are extensive in myometrial smooth muscle cells increasing its surface area by almost 75% (Somlyo 1985). CAVs act as a scaffold to congregate multiple proteins involved in calcium signalling and CON of smooth muscle contractions, including calcium channels, calcium-binding proteins, calcium pumps (Darby et al 2000) and calcium-sensitive potassium channels (Brainard et al 2005). The calcium-sensitive potassium channel provides a strong repolarising current to buffer cell excitation in response to excitatory cell signals (Jackson 2000), and inhibition of this channel pharmacologically during late pregnancy induces myometrial cell depolarisation and enhanced uterine contraction (Anwer et al 1993).…”

Section: Discussionmentioning

confidence: 99%

The effects of a high-fat, high-cholesterol diet on markers of uterine contractility during parturition in the rat

Elmes

Tan²,

Cheng³

et al. 2011

Reproduction

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Increasing levels of obesity within women of reproductive age is a major concern in the UK. Approximately, 13% of women aged !30 and 22% of 31-to 40-year-old women are obese. Obesity increases complications during pregnancy and the risk of caesarean section due to prolonged labour and poor uterine activity. The aim was to investigate whether a high-fat, high-cholesterol (HFHC) diet decreases markers of uterine contractility during parturition in the rat. Female Wistar rats were fed control (CON, nZ10) or HFHC (nZ10) diets for 6 weeks. Animals were mated and, once pregnant, maintained on their diet throughout gestation. On gestational day 19, rats were monitored continuously and killed at the onset of parturition. Body and fat depot weights were recorded. Myometrial tissue was analysed for cholesterol (CHOL), triglycerides (TAG), and expression of the contractile associated proteins gap junction protein alpha 1 (GJA1; also known as connexin-43, CX-43), prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclo-oxygenase-2, COX-2) and caveolin-1 (CAV1) and maternal plasma for prostaglandin F 2a (PGF 2a ) and progesterone. HFHC fed rats gained greater weight than CON (P!0.003) with significant increases in peri-renal fat (P!0.01). The HFHC diet increased plasma CHOL, TAG and progesterone, but decreased PGF 2a versus CON (P!0.01, P!0.01, PZ0.05 and P!0.02 respectively). Total CHOL and TAG levels of uterine tissue were similar. However, HFHC fed rats showed significant increases in PTGS2 (P!0.037), but decreases in GJA1 and CAV1 (PZ0.059). In conclusion, a HFHC diet significantly increases body weight and alters lipid profiles that correlate with decreases in key markers of uterine contractility. Further work is required to ascertain whether these changes have adverse effects on uterine activity.

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“…In the i16-containing mRNA knockdown experiments, we observed a radically different distribution where the BK Ca channel protein was far less likely to colocalize with filamentous actin in dendritic spines. Changes in BK Ca channels firing properties are synchronized with alterations in actin cytoskeletal dynamics (41) in some forms of stroke and epilepsy (40). One obvious question is to what extent neurons use an i16-containing mRNA to generate a functional BK Ca channel that can properly coordinate with the actin cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

Cytoplasmic BK _Ca channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons

Bell¹,

Miyashiro²,

Sul

et al. 2008

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

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High single-channel conductance K ؉ channels, which respond jointly to membrane depolarization and micromolar concentrations of intracellular Ca 2؉ ions, arise from extensive cell-specific alternative splicing of pore-forming ␣-subunit mRNAs. Here, we report the discovery of an endogenous BK Ca channel ␣-subunit intron-containing mRNA in the cytoplasm of hippocampal neurons. This partially processed mRNA, which comprises Ϸ10% of the total BK Ca channel ␣-subunit mRNAs, is distributed in a gradient throughout the somatodendritic space. We selectively reduced endogenous cytoplasmic levels of this intron-containing transcript by RNA interference without altering levels of the mature splice forms of the BK Ca channel mRNAs. In doing so, we could demonstrate that changes in a unique BK Ca channel ␣-subunit introncontaining splice variant mRNA can greatly impact the distribution of the BKCa channel protein to dendritic spines and intrinsic firing properties of hippocampal neurons. These data suggest a new regulatory mechanism for modulating the membrane properties and ion channel gradients of hippocampal neurons.dendrite ͉ epilepsy ͉ intron-retention ͉ KCNMA1 ͉ local splicing

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Maxi-K channels localize to caveolae in human myometrium: a role for an actin-channel-caveolin complex in the regulation of myometrial smooth muscle K⁺ current

Abstract: -K channels localize to caveolae in human myometrium: a role for an actin-channel-caveolin complex in the regulation of myometrial smooth muscle K ϩ current.

Cited by 109 publications

References 47 publications

Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

The effects of a high-fat, high-cholesterol diet on markers of uterine contractility during parturition in the rat

Cytoplasmic BK _Ca channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons

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Maxi-K channels localize to caveolae in human myometrium: a role for an actin-channel-caveolin complex in the regulation of myometrial smooth muscle K+ current

Abstract: -K channels localize to caveolae in human myometrium: a role for an actin-channel-caveolin complex in the regulation of myometrial smooth muscle K ϩ current.

Cited by 109 publications

References 47 publications

Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

Slo1 Caveolin-binding Motif, a Mechanism of Caveolin-1-Slo1 Interaction Regulating Slo1 Surface Expression

The effects of a high-fat, high-cholesterol diet on markers of uterine contractility during parturition in the rat

Cytoplasmic BK Ca channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons

Contact Info

Product

Resources

About

Maxi-K channels localize to caveolae in human myometrium: a role for an actin-channel-caveolin complex in the regulation of myometrial smooth muscle K⁺ current

Cytoplasmic BK _Ca channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons