Ca<sup>2+</sup>-Mobilization and Cell Contraction after Muscarinic Cholinergic Stimulation of the Chick Embryo Lens

Oppitz, Matthias; Mack, Andreas F.; Drews, Ulrich

doi:10.1167/iovs.03-0258

Cited by 13 publications

(12 citation statements)

References 19 publications

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“…The responding cells in our studies may correspond to the population of chicken annular pad cells responding to muscarinic acetycholine receptor stimulation with a [Ca 2ϩ ] i rise (Oppitz et al, 2003). We suggest that GABA and Ach may operate in concert as described previously for the chick retinal ventricular zone (Pearson et al, 2002) where the two neurotransmitters act synergistically to induce [Ca 2ϩ ] i rise.…”

Section: ؉ ] I In Equatorial Cells Of Intact Newborn Lensessupporting

confidence: 78%

GABA neurotransmitter signaling in the developing mouse lens: Dynamic regulation of components and functionality

Kwakowsky

Schwirtlich

Kooy

et al. 2008

Developmental Dynamics

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Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the vertebrate nervous system, serves as a signaling molecule modulating diverse processes during embryonic development. Earlier we have demonstrated that different forms of glutamic acid decarboxylase (GAD) are differentially regulated during mouse lens development. Here we show that the developing lens expresses also components of GABA signaling downstream of GAD. Multiple GABA A and GABA B receptor subunits as well as the GABA transporters show expression profiles highly correlated with the expression of different GADs. GABA receptors (GABAR) and the vesicular GABA transporter localize at the apical/basal membranes of the lens epithelia and differentiating fibers and may be involved in conventional GABAR-mediated signaling, while the membrane GABA transporters may also function as Na ؉ /Cl؊ /GABA carriers. The functionality of GABAR was verified by calcium imaging in whole lenses. Our data suggest that GABA synthesized locally by GAD, acts through GABA receptors by modulating the intracellular calcium levels. Developmental Dynamics 237:3830 -3841, 2008.

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Section: ؉ ] I In Equatorial Cells Of Intact Newborn Lensessupporting

confidence: 78%

GABA neurotransmitter signaling in the developing mouse lens: Dynamic regulation of components and functionality

Kwakowsky

Schwirtlich

Kooy

et al. 2008

Developmental Dynamics

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“…Striking functional and structural similarities between lens fiber cells and neurons are observed in the regulation of vesicle trafficking and the involvement of Alzheimer proteins in this process in the normal state and during disease (Frederikse and Zigler, 1998;Li et al, 2003;Frederikse et al, 2004). The spatiotemporal expression of GAD in the differentiating primary fiber cells of the mouse lens shows a remarkable similarity to the expression of choline acetyltransferase (Chat, the acetylcholine [ACh] -synthesizing enzyme) in chicken differentiating lens fibers (Oppitz et al, 2003). Especially noteworthy is the high accumulation of GAD and Chat at the apical and basal tips of the elongating fibers, suggesting that GABA may be involved in the reorganization of the cytoskeleton during fiber elongation, as suggested for ACh (Oppitz et al, 2003).…”

Section: Lens As a Model To Study The Nonsynaptic Gaba Signaling Durimentioning

confidence: 84%

“…The spatiotemporal expression of GAD in the differentiating primary fiber cells of the mouse lens shows a remarkable similarity to the expression of choline acetyltransferase (Chat, the acetylcholine [ACh] -synthesizing enzyme) in chicken differentiating lens fibers (Oppitz et al, 2003). Especially noteworthy is the high accumulation of GAD and Chat at the apical and basal tips of the elongating fibers, suggesting that GABA may be involved in the reorganization of the cytoskeleton during fiber elongation, as suggested for ACh (Oppitz et al, 2003). Finally, the lens affords a unique model to study the regulation of expression and intracellular role of multiple GAD isoforms, which, similar to the developing nervous system (Szabo et al, 1994;Katarova et al, 2000;Varju et al, 2001) are sequentially induced, but are spatiotemporally segregated.…”

Section: Lens As a Model To Study The Nonsynaptic Gaba Signaling Durimentioning

confidence: 99%

GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

Kwakowsky

Schwirtlich

Zhang

et al. 2007

Developmental Dynamics

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Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter of the adult nervous system and its biosynthetic enzyme glutamic acid decarboxylase (GAD) are abundantly expressed in the embryonic nervous system and are involved in the modulation of cell proliferation, migration, and differentiation. Here we describe for the first time the expression of GABA and embryonic and adult GAD isoforms in the developing mouse lens. We show that the GAD isoforms are sequentially induced with specific spatiotemporal profiles: GAD65 and embryonic GAD isoforms prevail in primary fibers, while GAD67 is the predominant GAD expressed in the postnatal secondary fibers. This pattern correlates well with the expression of Dlx2 and Dlx5, known as upstream regulators of GAD. GABA and GAD are most abundant at the tips of elongating fibers and are absent from organelle-free cells, suggesting their involvement is primarily in shaping of the cytoskeleton during fiber elongation stages. Developmental Dynamics 236: 3532-3544, 2007.

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“…Experiments with isolated lens vesicles of the chick embryo showed that the peak reaction of muscarinic-induced calcium mobilization was followed by a contraction of the whole lens [Oppitz et al, 2003]. Addition of atropine in the plateau phase released the contraction so that the lens vesicle returned to its original diameter.…”

Section: Discussionmentioning

confidence: 99%

Identification and Functional Characterization of the Muscarinic Receptor M3 in the Human Keratinocyte Cell Line HaCaT

Metzger

Just²,

Boss³

et al. 2005

Cells Tissues Organs

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In the epidermis muscarinic cholinergic receptors are expressed in keratinocytes during normal differentiation and in regeneration of the skin. The muscarinic receptors were implicated to regulate proliferation, migration and differentiation of keratinocytes. Therefore, we characterized the muscarinic receptor in the spontaneously immortalized human keratinocyte cell line HaCaT and studied its role in cell migration. By RT-PCR, Western blot and immunocytochemistry we show that HaCaT cells express the M3 receptor subtype. This receptor was further characterized by fluorometric measurement of calcium mobilization in cell suspensions. After muscarinic stimulation a peak reaction of intracellular calcium mobilization occurred followed by a plateau phase of extracellular influx which was reversible by atropine. In dose-response curves the effective concentrations of carbachol and acetylcholine were determined as 40 and 1 µM, respectively. The migratory activity of HaCaT cells was studied with the phagokinetic track assay. Treatment with the muscarinic agonist carbachol had no effect on cell migration. However, carbachol diminished the EGF-induced increase in migratory activity by about 26%. Interestingly, EGF and carbachol had additive effects on calcium mobilization.

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Ca²⁺-Mobilization and Cell Contraction after Muscarinic Cholinergic Stimulation of the Chick Embryo Lens

Cited by 13 publications

References 19 publications

GABA neurotransmitter signaling in the developing mouse lens: Dynamic regulation of components and functionality

GABA neurotransmitter signaling in the developing mouse lens: Dynamic regulation of components and functionality

GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

Identification and Functional Characterization of the Muscarinic Receptor M3 in the Human Keratinocyte Cell Line HaCaT

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Ca2+-Mobilization and Cell Contraction after Muscarinic Cholinergic Stimulation of the Chick Embryo Lens

Cited by 13 publications

References 19 publications

GABA neurotransmitter signaling in the developing mouse lens: Dynamic regulation of components and functionality

GABA neurotransmitter signaling in the developing mouse lens: Dynamic regulation of components and functionality

GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

Identification and Functional Characterization of the Muscarinic Receptor M3 in the Human Keratinocyte Cell Line HaCaT

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Ca²⁺-Mobilization and Cell Contraction after Muscarinic Cholinergic Stimulation of the Chick Embryo Lens