Depletion of calcium stores regulates calcium influx and signal transmission in rod photoreceptors

Szikra, Tamás; Cusato, K.; Thoreson, Wallace B.; Barabás, Péter; Bartoletti, Theodore M.; Križaj, David

doi:10.1113/jphysiol.2008.160051

Cited by 49 publications

(67 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After sequential image acquisition of cells' fluorescence at 495/440 nm or 340/380 nm, the backgrounds were subtracted using commercial software (Metafluor; Universal Imaging, West Chester, PA and NIS Elements, Melville, NY). Calibration of [Ca 2ϩ ]i and pHi was carried out as described previously (63)(64)(65)(66). Intracellular pH was calibrated from 495-to-440 ratios using the nigericin/high extracellular K ϩ method (10 M nigericin/90 mM KCl).…”

Section: Methodsmentioning

confidence: 99%

Intracellular pH modulates inner segment calcium homeostasis in vertebrate photoreceptors

Križaj

Mercer²,

Thoreson

et al. 2011

American Journal of Physiology-Cell Physiology

Self Cite

View full text Add to dashboard Cite

Neuronal metabolic and electrical activity is associated with shifts in intracellular pH (pH(i)) proton activity and state-dependent changes in activation of signaling pathways in the plasma membrane, cytosol, and intracellular compartments. We investigated interactions between two intracellular messenger ions, protons and calcium (Ca²(+)), in salamander photoreceptor inner segments loaded with Ca²(+) and pH indicator dyes. Resting cytosolic pH in rods and cones in HEPES-based saline was acidified by ∼0.4 pH units with respect to pH of the superfusing saline (pH = 7.6), indicating that dissociated inner segments experience continuous acid loading. Cytosolic alkalinization with ammonium chloride (NH₄Cl) depolarized photoreceptors and stimulated Ca²(+) release from internal stores, yet paradoxically also evoked dose-dependent, reversible decreases in [Ca²(+)](i). Alkalinization-evoked [Ca²(+)](i) decreases were independent of voltage-operated and store-operated Ca²(+) entry, plasma membrane Ca²(+) extrusion, and Ca²(+) sequestration into internal stores. The [Ca²(+)](i)-suppressive effects of alkalinization were antagonized by the fast Ca²(+) buffer BAPTA, suggesting that pH(i) directly regulates Ca²(+) binding to internal anionic sites. In summary, this data suggest that endogenously produced protons continually modulate the membrane potential, release from Ca²(+) stores, and intracellular Ca²(+) buffering in rod and cone inner segments.

show abstract

Section: Methodsmentioning

confidence: 99%

Intracellular pH modulates inner segment calcium homeostasis in vertebrate photoreceptors

Križaj

Mercer²,

Thoreson

et al. 2011

American Journal of Physiology-Cell Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nevertheless, the typical phenotypes of CNG channel deficiency are impaired opsin trafficking and opsin mislocalization (8,20), reflecting impaired ER function/protein folding, and ER stress. It is worth mentioning that there are other Ca 2ϩ channels in the inner segment membrane, including transient receptor potential channels, and these channels could also play a role in the cytosolic Ca 2ϩ regulation (42,43). entry is probably decreased) to compensate for the reduced cytosolic Ca 2ϩ level, which could potentially lead to a reduction of ER Ca 2ϩ level.…”

Section: Contribution Of Cgmp/pkg Signaling To Er Stress-cngmentioning

confidence: 99%

cGMP/Protein Kinase G Signaling Suppresses Inositol 1,4,5-Trisphosphate Receptor Phosphorylation and Promotes Endoplasmic Reticulum Stress in Photoreceptors of Cyclic Nucleotide-gated Channel-deficient Mice

Butler

Thapa

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Cone photoreceptors undergo endoplasmic reticulum stress-associated apoptosis in CNG channel deficiency. Results: Suppressing cGMP/PKG signaling enhances inositol 1,4,5-trisphosphate receptor 1 (IP 3 R1) phosphorylation and inhibits endoplasmic reticulum stress and cone death. Conclusion: cGMP/PKG signaling regulates IP 3 R1 activity and promotes endoplasmic reticulum stress in CNG channel deficiency. Significance: Understanding of the mechanism(s) of photoreceptor degeneration is essential for therapeutic strategy development.

show abstract

“…In mouse retina, TRPC1 was expressed in rods and cones and rod store-operated Ca 2+ entry was unaffected in Trpc1-null mice, indicating that TRPC1 does not regulate light-evoked responses at the mouse rod output synapse (Molnar et al 2012). However, downregulation of TRPC1 by RNAi did suppress storeoperated Ca 2+ entry in rods (Szikra et al 2008). The reasons for these discrepancies are unknown but could stem from inherent differences between acute (RNAi in vitro) and chronic (knockout in vivo) gene ablation.…”

mentioning

confidence: 84%

Trpc1

Nesin

Tsiokas

2014

Handbook of Experimental Pharmacology

View full text Add to dashboard Cite

The TRPC1 ion channel was the first mammalian TRP channel to be cloned. In humans, it is encoded by the TRPC1 gene located in chromosome 3. The protein is predicted to consist of six transmembrane segments with the N- and C-termini located in the cytoplasm. The extracellular loop connecting transmembrane segments 5 and 6 participates in the formation of the ionic pore region. Inside the cell, TRPC1 is present in the endoplasmic reticulum, plasma membrane, intracellular vesicles, and primary cilium, an antenna-like sensory organelle functioning as a signaling platform. In human and rodent tissues, it shows an almost ubiquitous expression. TRPC1 interacts with a diverse group of proteins including ion channel subunits, receptors, and cytosolic proteins to mediate its effect on Ca(2+) signaling. It primarily functions as a cation nonselective channel within pathways controlling Ca(2+) entry in response to cell surface receptor activation. Through these pathways, it affects basic cell functions, such as proliferation and survival, differentiation, secretion, and cell migration, as well as cell type-specific functions such as chemotropic turning of neuronal growth cones and myoblast fusion. The biological role of TRPC1 has been studied in genetically engineered mice where the Trpc1 gene has been experimentally ablated. Although these mice live to adulthood, they show defects in several organs and tissues, such as the cardiovascular, central nervous, skeletal and muscular, and immune systems. Genetic and functional studies have implicated TRPC1 in diabetic nephropathy, Parkinson's disease, Huntington's disease, Duchenne muscular dystrophy, cancer, seizures, and Darier-White skin disease.

show abstract

Depletion of calcium stores regulates calcium influx and signal transmission in rod photoreceptors

Cited by 49 publications

References 81 publications

Intracellular pH modulates inner segment calcium homeostasis in vertebrate photoreceptors

Intracellular pH modulates inner segment calcium homeostasis in vertebrate photoreceptors

cGMP/Protein Kinase G Signaling Suppresses Inositol 1,4,5-Trisphosphate Receptor Phosphorylation and Promotes Endoplasmic Reticulum Stress in Photoreceptors of Cyclic Nucleotide-gated Channel-deficient Mice

Trpc1

Contact Info

Product

Resources

About