Functional Expression of Inward Rectifier Potassium Channels in Cultured Human Pulmonary Smooth Muscle Cells: Evidence for a Major Role of Kir2.4 Subunits

Tennant, Brian P.; Cui, Yi; Tinker, Andrew

doi:10.1007/s00232-006-0037-y

Cited by 29 publications

(19 citation statements)

References 39 publications

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“…Moreover, K IR 2.1 appeared to be involved in the K + -mediated vasodilation in contrast to K IR 2.2 (Zaritsky et al 2000). However, apart from K IR 2.1, Tennant et al (2006) reported a predominant role for K IR 2.4 in cultured human pulmonary artery smooth muscle cells.…”

Section: Functional Expression Of K Ir 2xmentioning

confidence: 86%

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The mammalian K_IR2.x inward rectifier ion channel family: expression pattern and pathophysiology

Boer¹,

Houtman²,

Compier³

et al. 2010

Acta Physiologica

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Inward rectifier currents based on K(IR)2.x subunits are regarded as essential components for establishing a stable and negative resting membrane potential in many excitable cell types. Pharmacological inhibition, null mutation in mice and dominant positive and negative mutations in patients reveal some of the important functions of these channels in their native tissues. Here we review the complex mammalian expression pattern of K(IR)2.x subunits and relate these to the outcomes of functional inhibition of the resultant channels. Correlations between expression and function in muscle and bone tissue are observed, while we recognize a discrepancy between neuronal expression and function.

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Section: Functional Expression Of K Ir 2xmentioning

confidence: 86%

“…2000). However, apart from K IR 2.1, Tennant et al. (2006) reported a predominant role for K IR 2.4 in cultured human pulmonary artery smooth muscle cells.…”

Section: Kir2x Expression Profilesmentioning

confidence: 89%

The mammalian K_IR2.x inward rectifier ion channel family: expression pattern and pathophysiology

Boer¹,

Houtman²,

Compier³

et al. 2010

Acta Physiologica

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“…For the experiments, MSCs were grown in 96‐ or 6‐well culture plates or on glass coverslips (placed on the bottom of a well of a 6 well‐plates), stimulated or not (control) with diode laser (time 0, T0), and cultured in growth medium for 24, 48, and 72 h. During laser irradiation the cells were incubated in Red Phenol free medium (GIBCO™, Invitrogen). In some experiments MSCs were treated with 0.5 mM BaCl 2 for 24 h prior laser irradiation in order to inhibit Kir channels (Tennant et al, 2006; Ma et al, 2011).…”

Section: Methodsmentioning

confidence: 99%

“…The occurrence of the Kir current was assessed in voltage‐clamp by recording the currents in response to voltage ramps ranging from −120 to 50 mV over a period of 0.5 sec, which were imposed every 1 min from a holding potential of −60 mV and digitized at a rate of 5 kHz; two runs repeated every 20 sec were averaged. First, we used the control physiological solution without Ba 2+ (control) to record any K + current (I K,DR and I Kir ) followed by Ba 2+ addition to block I Kir (Tennant et al, 2006; Ma et al, 2011). Finally, the average of two ramps elicited in the presence of Ba 2+ was subtracted from control currents to evaluate I Kir .…”

Section: Methodsmentioning

confidence: 99%

Photoactivation of bone marrow mesenchymal stromal cells with diode laser: Effects and mechanisms of action

Giannelli

Chellini

Sassoli

et al. 2012

Journal Cellular Physiology

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Mesenchymal stromal cells (MSCs) are a promising cell candidate in tissue engineering and regenerative medicine. Their proliferative potential can be increased by low-level laser irradiation (LLLI), but the mechanisms involved remain to be clarified. With the aim of expanding the therapeutic application of LLLI to MSC therapy, in the present study we investigated the effects of 635 nm diode laser on mouse MSC proliferation and investigated the underlying cellular and molecular mechanisms, focusing the attention on the effects of laser irradiation on Notch-1 signal activation and membrane ion channel modulation. It was found that MSC proliferation was significantly enhanced after laser irradiation, as judged by time lapse videomicroscopy and EdU incorporation. This phenomenon was associated with the up-regulation and activation of Notch-1 pathway, and with increased membrane conductance through voltage-gated K(+) , BK and Kir, channels and T- and L-type Ca(2+) channels. We also showed that MSC proliferation was mainly dependent on Kir channel activity, on the basis that the cell growth and Notch-1 up-regulation were severely decreased by the pre-treatment with the channel inhibitor Ba(2+) (0.5 mM). Interestingly, the channel inhibition was also able to attenuate the stimulatory effects of diode laser on MSCs, thus providing novel evidence to expand our knowledge on the mechanisms of biostimulation after LLLI. In conclusions, our findings suggest that diode laser may be a valid approach for the preconditioning of MSCs in vitro prior cell transplantation.

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“…Potassium channels regulate the resting membrane potential of pulmonary artery smooth muscle cells. [31][32][33] Voltage-gated potassium channels are involved in the hypoxic pulmonary vasoconstrictive response, 34 while downregulation of K v channel expression in PASMCs of PAH patients promotes PASMC excitability and proliferation, and excessive pulmonary arterial vasoconstriction. 20,35,36 Potassium channel openers may provide therapeutic benefit by opposing such deleterious pulmonary arterial remodeling 37 ; recently, pharmacological KCNK3 activation by ONO-RS-082 (ONO) attenuated development of pulmonary hypertension in a monocrotalineinduced rat model.…”

Section: Mutant and Wt Kcnk3 Channels Are Pharmacological Targets In mentioning

confidence: 99%

The Impact of Heterozygous KCNK3 Mutations Associated With Pulmonary Arterial Hypertension on Channel Function and Pharmacological Recovery

Bohnen

Roman‐Campos

Terrenoire

et al. 2017

JAHA

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BackgroundHeterozygous loss of function mutations in the KCNK3 gene cause hereditary pulmonary arterial hypertension (PAH). KCNK3 encodes an acid‐sensitive potassium channel, which contributes to the resting potential of human pulmonary artery smooth muscle cells. KCNK3 is widely expressed in the body, and dimerizes with other KCNK3 subunits, or the closely related, acid‐sensitive KCNK9 channel.Methods and ResultsWe engineered homomeric and heterodimeric mutant and nonmutant KCNK3 channels associated with PAH. Using whole‐cell patch‐clamp electrophysiology in human pulmonary artery smooth muscle and COS7 cell lines, we determined that homomeric and heterodimeric mutant channels in heterozygous KCNK3 conditions lead to mutation‐specific severity of channel dysfunction. Both wildtype and mutant KCNK3 channels were activated by ONO‐RS‐082 (10 μmol/L), causing cell hyperpolarization. We observed robust gene expression of KCNK3 in healthy and familial PAH patient lungs, but no quantifiable expression of KCNK9, and demonstrated in functional studies that KCNK9 minimizes the impact of select KCNK3 mutations when the 2 channel subunits co‐assemble.ConclusionsHeterozygous KCNK3 mutations in PAH lead to variable loss of channel function via distinct mechanisms. Homomeric and heterodimeric mutant KCNK3 channels represent novel therapeutic substrates in PAH. Pharmacological and pH‐dependent activation of wildtype and mutant KCNK3 channels in pulmonary artery smooth muscle cells leads to membrane hyperpolarization. Co‐assembly of KCNK3 with KCNK9 subunits may provide protection against KCNK3 loss of function in tissues where both KCNK9 and KCNK3 are expressed, contributing to the lung‐specific phenotype observed clinically in patients with PAH because of KCNK3 mutations.

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Functional Expression of Inward Rectifier Potassium Channels in Cultured Human Pulmonary Smooth Muscle Cells: Evidence for a Major Role of Kir2.4 Subunits

Abstract: Strong inwardly rectifying K + (K IR ) channels that contribute to maintaining the resting membrane potential are encoded by the Kir2.0 family (Kir2

Cited by 29 publications

References 39 publications

The mammalian K_IR2.x inward rectifier ion channel family: expression pattern and pathophysiology

The mammalian K_IR2.x inward rectifier ion channel family: expression pattern and pathophysiology

Photoactivation of bone marrow mesenchymal stromal cells with diode laser: Effects and mechanisms of action

The Impact of Heterozygous KCNK3 Mutations Associated With Pulmonary Arterial Hypertension on Channel Function and Pharmacological Recovery

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Functional Expression of Inward Rectifier Potassium Channels in Cultured Human Pulmonary Smooth Muscle Cells: Evidence for a Major Role of Kir2.4 Subunits

Abstract: Strong inwardly rectifying K + (K IR ) channels that contribute to maintaining the resting membrane potential are encoded by the Kir2.0 family (Kir2

Cited by 29 publications

References 39 publications

The mammalian KIR2.x inward rectifier ion channel family: expression pattern and pathophysiology

The mammalian KIR2.x inward rectifier ion channel family: expression pattern and pathophysiology

Photoactivation of bone marrow mesenchymal stromal cells with diode laser: Effects and mechanisms of action

The Impact of Heterozygous KCNK3 Mutations Associated With Pulmonary Arterial Hypertension on Channel Function and Pharmacological Recovery

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Product

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The mammalian K_IR2.x inward rectifier ion channel family: expression pattern and pathophysiology

The mammalian K_IR2.x inward rectifier ion channel family: expression pattern and pathophysiology