KCa3.1 Ca2+Activated K+ Channels Regulate Human Airway Smooth Muscle Proliferation

Shepherd, Malcolm; Duffy, S. Mark; Harris, Trudi; Cruse, Glenn; Schuliga, Michael; Brightling, Christopher E.; Neylon, Craig B.; Bradding, Peter; Stewart, Alastair G.

doi:10.1165/rcmb.2006-0358oc

Cited by 74 publications

(97 citation statements)

References 51 publications

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“…Increasing evidence also supports a prominent role of KCa3.1 in respiratory diseases such as allergic asthma (8) and airway obstruction coming from tissues remodeling (8,9). These data add to the compelling observations that KCa3.1 is important for fluid secretion in epithelial cells by maintaining an electrochemical gradient favorable to Cl Ϫ and Na ϩ transepithelial transport.…”

mentioning

confidence: 66%

Hydrophobic Interactions as Key Determinants to the KCa3.1 Channel Closed Configuration

Garneau¹,

Klein²,

Banderali³

et al. 2009

Journal of Biological Chemistry

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mentioning

confidence: 66%

Hydrophobic Interactions as Key Determinants to the KCa3.1 Channel Closed Configuration

Garneau¹,

Klein²,

Banderali³

et al. 2009

Journal of Biological Chemistry

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“…In Davie et al (24) study, cicaprost inhibited ET-1 release from PASMCs, increased cAMP levels and suppressed DNA synthesis; (ii) modafinil shows an antiproliferative effect by the reduction of KCa3.1 channel expression in PASMCs in the lung tissues. This hypothesis was based on a previous report that KCa3.1 channel is involved in airway smooth muscle (22).…”

Section: Discussionmentioning

confidence: 99%

“…There are several studies about the effect of KCa3.1 channels blocker on human lung mast cell proliferation and migration (21,22). However, there have not been any reports about the effect of modafinil on PASMCs proliferation.…”

mentioning

confidence: 99%

Modafinil improves monocrotaline-induced pulmonary hypertension rat model

et al. 2016

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Background: Pulmonary arterial hypertension (PAH) progressively leads to increases in pulmonary vasoconstriction. Modafinil plays a role in vasorelaxation and blocking KCa3.1 channel with a result of elevating intracellular cyclic adenosine monophosphate (cAMP) levels. The purpose of this study is to evaluate the effects on modafinil in monocrotaline (MCT)-induced PAH rat. Methods: The rats were separated into three groups: the control group, the monocrotaline (M) group (MCT 60 mg/kg), and the modafinil (MD) group (MCT 60 mg/kg + modafinil). results: Reduced right ventricular pressure (RVP) was observed in the MD group. Right ventricular hypertrophy was improved in the MD group. Reduced number of intra-acinar pulmonary arteries and medial wall thickness were noted in the MD group. After the administration of modafinil, protein expressions of endothelin-1 (ET-1), endothelin receptor A (ERA) and KCa3.1 channel were significantly reduced. Modafinil suppressed pulmonary artery smooth muscle cell (PASMC) proliferation via cAMP and KCa3.1 channel. Additionally, we confirmed protein expressions such as Bcl-2-associated X, vascular endothelial growth factor, tumor necrosis factor-α, and interleukin-6 were reduced in the MD group. conclusion: Modafinil improved PAH by vasorelaxation and a decrease in medial thickening via ET-1, ERA, and KCa3.1 down regulation. This is a meaningful study of a modafinil in PAH model.

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“…Finally, TRAM-34 is a highly specific small molecule blocker of KCa3.1 that does not affect cytochrome P450. TRAM-34 has low toxicity and causes minimal cell death and apoptosis (10,24). If the role of KCa3.1 in DC migration under inflammatory condition is further established in an in vivo study, TRAM-34 could be a potential drug that targets KCa3.1.…”

Section: Discussionmentioning

confidence: 99%

“…It is expressed in almost all types of migrating cells (9), including airway smooth muscle cells (10), vascular smooth muscle cells (11)(12)(13), T cells (14), macrophages (15), and mast cells (16). Functionally, KCa3.1 plays a key role in calcium-dependent cell functions, such as proliferation, activation, and migration, in a broad range of cell types.…”

mentioning

confidence: 99%