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Ca2+ responses to hypoxia are mediated by IP3-R on Ca2+ store depletion

  • Sukhamay Lahiri
  • Arijit Roy
  • Jinquing Li
  • Anil Mokashi
  • Santhosh M. Baby
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 536)

Abstract

Inositol 1,4, 5-triphosphate (IP3) is generated from the hydrolysis of phosphatidylinositol 4, 5-triphosphate (PIP2) which is a component of plasma membrane. IP3 acts as a messenger to link with receptors IP3-Rs which are located on intracellular Ca2+ stores, such as the endoplasmic reticulum (ER) (Belousov et al., 1995; Berridge, 1993). The ER also often shares the same domain of the mitochondria which have a low affinity, high-capacity for Ca2+ uptake mechanism, and Ca2+ concentrations influence mitochondrial metabolism (Duchen, 2000). Thus, IP3-Rs are an ideal candidate for Ca2+- related cellular functions, Rizzuto et al. (1993) have shown that [Ca2+]m increases rapidly and transiently upon stimulation with agonists coupled to IP3- R generation. This leads to high [Ca2+]i close to IP3-R and sensed by mitochondria. Conversely, metabolites generated by energy production may influence IP3-mediated Ca2+ dynamics. Depletion of cellular energy resources leads to the accumulation of cytoplasmic reduced NADH (Veech et al., 1970). Hypoxia decreases mitochondrial respiration by inhibiting the terminal step in the electron transport chains, provoking a rapid rise in intracellular Ca2+ (Biscoe and Duchen, 1990; Kaplin et al., 1996; McCormack et al., 1990). Hypoxia also increases cytoplasmic NADH levels as a result of enhanced glycolysis (Yager et al., 1991). Also, NADH selectively stimulates the release of Ca2+ mediated by IP3-R (Ferris and Snyder, 1992).

Keywords

Carotid Body Hypoxic Response Inositol Trisphosphate Glomus Cell Store Depletion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Sukhamay Lahiri
    • 1
  • Arijit Roy
    • 1
  • Jinquing Li
    • 1
  • Anil Mokashi
    • 1
  • Santhosh M. Baby
    • 1
  1. 1.Department of PhysiologyUniversity of Pennsylvania Medical CenterPhiladelphiaUSA

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