Hypotonicity activates a native chloride current in Xenopus oocytes.

Ackerman, Michael J.; Wickman, Kevin; Clapham, David E.

doi:10.1085/jgp.103.2.153

Cited by 211 publications

(152 citation statements)

References 70 publications

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“…Defolliculated oocytes were thoroughly monitored for endogenous swelling-activated whole-cell currents as reported earlier (33). Three days after injection, oocyte rupture and volume-activated whole-cell currents were virtually absent in waterinjected control oocytes, similar to earlier studies (34).…”

Section: Best1 Deficiency In the Mouse Impairs Sperm Function And Ressupporting

confidence: 68%

“…Capped RNA was synthesized by in vitro transcription with Sp6 RNA polymerase. Ooctyes from X. laevis were prepared as described (33) and were thoroughly defolliculated and monitored for endogenous swelling-activity. Membrane currents were measured by voltage clamping (oocyte clamp amplifier; Warner Instruments LLC) in intervals from −80 to +60 mV, in steps of 20 mV, each 1 s (SI Materials and Methods).…”

Section: Methodsmentioning

confidence: 99%

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Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells

Milenkovic¹,

Brandl

Milenkovic³

et al. 2015

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

113

142

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In response to cell swelling, volume-regulated anion channels (VRACs) participate in a process known as regulatory volume decrease (RVD). Only recently, first insight into the molecular identity of mammalian VRACs was obtained by the discovery of the leucine-rich repeats containing 8A (LRRC8A) gene. Here, we show that bestrophin 1 (BEST1) but not LRRC8A is crucial for volume regulation in human retinal pigment epithelium (RPE) cells. Whole-cell patch-clamp recordings in RPE derived from human-induced pluripotent stem cells (hiPSC) exhibit an outwardly rectifying chloride current with characteristic functional properties of VRACs. This current is severely reduced in hiPSC-RPE cells derived from macular dystrophy patients with pathologic BEST1 mutations. Disruption of the orthologous mouse gene (Best1 −/− ) does not result in obvious retinal pathology but leads to a severe subfertility phenotype in agreement with minor endogenous expression of Best1 in murine RPE but highly abundant expression in mouse testis. Sperm from Best1 −/− mice showed reduced motility and abnormal sperm morphology, indicating an inability in RVD. Together, our data suggest that the molecular identity of VRACs is more complex-that is, instead of a single ubiquitous channel, VRACs could be formed by cell type-or tissue-specific subunit composition. Our findings provide the basis to further examine VRAC diversity in normal and diseased cell physiology, which is key to exploring novel therapeutic approaches in VRAC-associated pathologies.bestrophin 1 | volume-regulated anion channel | induced pluripotent stem cell | retinal pigment epithelium | mouse sperm

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Section: Best1 Deficiency In the Mouse Impairs Sperm Function And Ressupporting

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells

Milenkovic¹,

Brandl

Milenkovic³

et al. 2015

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

113

142

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“…The standard bath recording solution contained (in mM) 96 NaCl, 1 KCl, 1.8 CaCl 2 , and 0.1 LaCl 3 with the pH adjusted to 7.5 or 4.5. LaCl 3 was included in the bath solution as it effectively attenuates potential voltage-dependent, hyperpolarization-induced, and volume-sensitive endogenous oocyte chloride currents (Ackerman et al, 1994;Tokimasa and North, 1996). The latter approach has been successful for the characterization of inward currents mediated by several members of the ALMT family of transporters (Hoekenga et al, 2006;Piñeros et al, 2008a;Ligaba et al, 2012).…”

Section: Functional Characterization Of Gmalmt1 In Xenopus Laevis Oocmentioning

confidence: 99%

Low pH, Aluminum, and Phosphorus Coordinately Regulate Malate Exudation through GmALMT1 to Improve Soybean Adaptation to Acid Soils

et al. 2013

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Low pH, aluminum (Al) toxicity, and low phosphorus (P) often coexist and are heterogeneously distributed in acid soils. To date, the underlying mechanisms of crop adaptation to these multiple factors on acid soils remain poorly understood. In this study, we found that P addition to acid soils could stimulate Al tolerance, especially for the P-efficient genotype HN89. Subsequent hydroponic studies demonstrated that solution pH, Al, and P levels coordinately altered soybean (Glycine max) root growth and malate exudation. Interestingly, HN89 released more malate under conditions mimicking acid soils (low pH, +P, and +Al), suggesting that root malate exudation might be critical for soybean adaptation to both Al toxicity and P deficiency on acid soils. GmALMT1, a soybean malate transporter gene, was cloned from the Al-treated root tips of HN89. Like root malate exudation, GmALMT1 expression was also pH dependent, being suppressed by low pH but enhanced by Al plus P addition in roots of HN89. Quantitative real-time PCR, transient expression of a GmALMT1-yellow fluorescent protein chimera in Arabidopsis protoplasts, and electrophysiological analysis of Xenopus laevis oocytes expressing GmALMT1 demonstrated that GmALMT1 encodes a root cell plasma membrane transporter that mediates malate efflux in an extracellular pH-dependent and Al-independent manner. Overexpression of GmALMT1 in transgenic Arabidopsis, as well as overexpression and knockdown of GmALMT1 in transgenic soybean hairy roots, indicated that GmALMT1-mediated root malate efflux does underlie soybean Al tolerance. Taken together, our results suggest that malate exudation is an important component of soybean adaptation to acid soils and is coordinately regulated by three factors, pH, Al, and P, through the regulation of GmALMT1 expression and GmALMT1 function.

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“…One basis for this difference is that some cells may possess large excess membrane reserves in the form of folds microvilli and caveola (e.g., Xenopus oocytes and skeletal muscle) that can buffer rapid increases in bilayer tension Hamill 2000a, 2000b;. Conversely, not all channels activated by cell swelling are activated by membrane stretch when applied to the patch (Ackerman et al 1994;Strotmann et al 2000).…”

Section: Osmotic Swelling and Cell Inflationmentioning

confidence: 99%

“…It should also be recognized that cell swelling does not always activate MscCa. For example, although hypotonic solution activates a robust Ca 2+ -independent Cl − conductance in Xenopus oocytes that should contribute to RVD, it fails to activate the endogenous MscCa (Ackerman et al 1994;Zhang and Hamill 2000a). …”

Section: Trpc1 and Volume Regulationmentioning

confidence: 99%

The Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness

Hamill¹

2011

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)2. REPORT TYPE 3. DATES COVERED (From -To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail:5f. WORK UNIT NUMBER 4 Introduction A major challenge for treating prostate cancer (PC) is to discover new therapies that will prevent the spread of PC cells from the prostate to distal sites. Our research focuses on the stretch-activated mechanosensitive Ca 2+ permeant channel (MscCa) as a central regulator of prostate tumor cell migration. Our experiments are designed to address the two most basic issues of the disease: the mechanism(s) that trigger progression of PC to malignancy and the urgent need for new therapeutic targets to block or reverse this progression. Our original experiments funded by DOD were aimed to test whether MscCa is expressed in human prostate tumor cells and whether MscCa activity is required for prostate tumor cell migration. We confirmed both results. In the course of these experiments we also discovered that the predominate gating mode of the MscCa differs between noninvasive and invasive PC cells, may be the most powerful determinate of the [Ca 2+ ]i dynamics required to coordinate cell locomotion. The aims of the current award were three-fold. First, determine the mechanisms underlying MscCa gating. Second, determine the cancer-related processes that switch MscCa gating, and third determine whether anti-MscCa conditions that suppress PC migration in vitro also block PC cell invasion in vivo. Insights into these aspects would provide added motivation for developing more selective therapies that target MscCa and its regulatory mechanisms. The basic results supporting our hypothesis have been published (Maroto, R. & Hamill, O.P. MscCa regulation of tumor cell migration and metastasis. Current Topics in Membranes.59, 485-509, 2007). Also included in the Appendix are other manuscripts and abstracts Gotlieb et al., 2008; Maroto & Hamill, 2011; and Maroto, Kurosky and Hamill, 2011) that include specific results described in body of the text. PERFORMING ORGANIZATION NAME(S) AND AD...

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Hypotonicity activates a native chloride current in Xenopus oocytes.

Cited by 211 publications

References 70 publications

Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells

Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells

Low pH, Aluminum, and Phosphorus Coordinately Regulate Malate Exudation through GmALMT1 to Improve Soybean Adaptation to Acid Soils

The Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness

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