Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2010; 56(4): 130-138

Alteration of calcium signaling as one of the mechanisms of Alzheimer's disease and diabetic polyneuropathy

Kostiuk OP, Korol' TIu, Korol' SV, Romanenko SV, Pinchenko VO, Kostiuk PH

    O.O.Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine


This review is devoted to the action of amyloid-b peptide on the functional activity of intracellular and plasmalemmal calcium-regulated structures in cultured hyppocampal neurons: mitochondria and voltage-gated calcium channels. A comparative analysis of relative changes of plasmalemmal structures in such neurodegenerative diseases as Alzheimer’s illness and diabetic neuropathy has been made.

Keywords: mitochondrion, Alzheimer’s disease, diabetic neuropathy, neurodegenerative disease, neurons, hippocampus, plasmalemal calcium channels, calcium.


  1. Kostyuk P.G., Zima V.L., Magura I.C., Miroshnichenko M.S., Shuba M.F. Biofizika. K.: Oberegi, 2008. 544 c.
  3. Yahno N.N., Preobrazhenskaya I.S. Bolezn' Al'ts-geimera: patogenez, klinika, lechenie . Rus. med.zhurn. 2002. 10. P. 1143-1146.
  5. Anand U., Otto W.R., Casula M.A., Day N.C., Davis J.B., Bountra C., Birch R.,Anand P. The effect of neurotrophic factors on morphology, TRPV1 expres­sion and capsaicin responses of cultured human DRG sensory neurons . Neurosci.Lett. 2006. 399. P. 51-56. CrossRef PubMed
  7. Arispe N., Rojas E.,Pollard H.B. Alzheimer disease amyloid beta protein forms calcium channels in bi-layer membranes: blockade by tromethamine and aluminum . Proc.Natl.Acad.Sci.USA. 1993. 90. P. 567-571. CrossRef PubMed PubMedCentral
  9. Caterina M.J., Schumacher M.A., Tominaga M., Rosen T.A., Levine J.D.Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway . Na­ture. 1997. 389. P. 816-824. CrossRef PubMed
  11. Cesare P., McNaughton P. A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin . Proc.Natl.Acad.Sci.USA. 1996. 93. P. 15435-15439. CrossRef PubMed PubMedCentral
  13. Clapham D.E. TRP channels as cellular sensors . Na­ture. 2003. 426. P. 517-524. CrossRef PubMed
  15. Cook D.G., Li X., Cherry S.D.,Cantrell A.R. Presenilin 1 deficiency alters the activity of voltage-gated Ca2+ channels in cultured cortical neurons . J.Neurophysiol. 2005. 94. P. 4421-4429. CrossRef PubMed
  17. Davidson R.M., Shajenko L.,Donta T.S. Amyloid beta-peptide (A beta P) potentiates a nimodipine-sensitive L-type barium conductance in N1E-115 neuroblastomacells . Brain Res. 1994. 643. P. 324-327. CrossRef  
  18. Hooper N.M. Alzheimer's disease: methods and pro­tocols.: Humana press Inc, 2002.
  20. Furukawa K., Abe Y.,Akaike N. Amyloid beta protein-induced irreversible current in rat cortical neurones . Neuroreport. 1994. 5. P. 2016-2018. CrossRef PubMed
  22. Gibson G.E., Sheu K.F.,Blass J.P. Abnormalities of mitochondrial enzymes in Alzheimer disease . J.Neural Transm. 1998. 105. P. 855-870. CrossRef PubMed
  24. He L.M., Chen L.Y., Lou X.L., Qu A.L., Zhou Z.,Xu T. Evaluation of beta-amyloid peptide 25-35 on calcium homeostasis in cultured rat dorsal root gan­glion neurons . Brain Res. 2002. 939. P. 65-75. CrossRef  
  25. Hirai K., Aliev G., Nunomura A., Fujioka H., Russell R.L., Atwood C.S., Johnson A.B., Kress Y. , Vinters H.V., Tabaton M., Shimohama S., Cash A.D., Siedlak S.L., Harris P.L., Jones P.K., Petersen R.B., Perry G.,Smith M.A. Mitochondrial abnormalities in Alzheimer's disease . J.Neurosci. 2001. 21. P. 3017-3023. CrossRef PubMed PubMedCentral
  27. Hu H.J., Bhave G.,Gereau R.W. Prostaglandin and pro­tein kinase A-dependent modulation of vanilloid receptor function by metabotropic glutamate receptor 5: potential mechanism for thermal hyperalgesia . J.Neurosci. 2002. 22. P. 7444-7452. CrossRef PubMed PubMedCentral
  29. Kang J., Lemaire H.G., Unterbeck A., Salbaum J.M., Masters C.L., Grzeschik K.H., Multhaup G., Beyreuther K.,Muller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor . Nature. 1987. 325. P. 733-736. CrossRef PubMed
  31. Kawahara M., Kuroda Y. Molecular mechanism of neurodegeneration induced by Alzheimer's beta-amy­loid protein: channel formation and disruption of calcium homeostasis . Brain Res.Bull. 2000. 53. P. 389-397. CrossRef  
  32. Kim B.M., Lee S.H., Shim W.S.,Oh U. Histamine-in-duced Ca(2+) influx via the PLA(2). lipoxygenase. TRPV1 pathway in rat sensory neurons . Neurosci. Lett. 2004. 361. P. 159-162. CrossRef PubMed
  34. Korol' T.I., Kostiuk O.P.,Kostiuk P.H. Effect of beta-amyloid protein on calcium channels in plasma membranes of cultured hippocampal neurons . Fiziol.Zh. 2009. 55. P. 10-16.
  36. Leissring M.A., Paul B.A., Parker I., Cotman C.W.,LaFerla F.M. Alzheimer's presenilin-1 mutation potentiates inositol 1,4,5-trisphosphate-mediated calcium signaling in Xenopus oocytes . J.Neurochem. 1999. 72. P. 1061-1068. CrossRef PubMed
  38. Li W.Y., Butler J.P., Hale J.E., McClure D.B., Little S.P., Czilli D.L.,Simmons L.K. Suppression of an amy­loid beta peptide-mediated calcium channel response by a secreted beta-amyloid precursor protein . Neuroscience. 2000. 95. P. 1-4. CrossRef  
  39. Lopshire J.C., Nicol G.D. The cAMP transduction cascade mediates the prostaglandin E2 enhancement of the capsaicin-elicited current in rat sensory neurons: whole-cell and single-channel studies . J.Neurosci. 1998. 18. P. 6081-6092. CrossRef PubMed PubMedCentral
  41. Marinelli S., Vaughan C.W., Christie M.J.,Connor M. Capsaicin activation of glutamatergic synaptic trans­mission in the rat locus coeruleus in vitro . J.Physiol. 2002. 543. P. 531-540. CrossRef PubMed PubMedCentral
  43. Mark R.J., Pang Z., Geddes J.W., Uchida K.,Mattson M.P. Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipid peroxidation . J.Neurosci. 1997. 17. P. 1046-1054. CrossRef PubMed PubMedCentral
  45. Masters C.L., Simms G., Weinman N.A., Mult-haup G., McDonald B.L.,Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome . Proc.Natl.Acad.Sci.USA. 1985. 82. P. 4245-4249. CrossRef PubMed PubMedCentral
  47. Moriyama T., Higashi T., Togashi K., Iida T., Segi E., Sugimoto Y., Tominaga T., Narumiya S.,Tominaga M. Sensitization of TRPV1 by EP1 and IP reveals periph­eral nociceptive mechanism of prostaglandins . Mol.Pain. 2005. 1. P. 3. CrossRef PubMed PubMedCentral
  49. Nilius B., Owsianik G., Voets T.,Peters J.A. Transient receptor potential cation channels in disease . Physiol Rev. 2007. 87. P. 165-217. CrossRef PubMed
  51. Pabbidi R.M., Yu S.Q., Peng S., Khardori R., Pauza M.E.,Premkumar L.S. Influence of TRPV1 on diabe­tes-induced alterations in thermal pain sensitivity . Mol.Pain. 2008. 4. P. 9. CrossRef PubMed PubMedCentral
  53. Pegorini S., Braida D., Verzoni C., Guerini-Rocco C., Consalez G.G., Croci L.,Sala M. Capsaicin ex­hibits neuroprotective effects in a model of transient global cerebral ischemia in Mongolian gerbils . Brit.J.Pharmacol. 2005. 144. P. 727-735. CrossRef PubMed PubMedCentral
  55. Ramsden M., Henderson Z.,Pearson H.A. Modulation of Ca2+ channel currents in primary cultures of rat cortical neurones by amyloid beta protein (1-40) is dependent on solubility status . Brain Res. 2002. 956. P. 254-261. CrossRef  
  56. Resende R., Pereira C., Agostinho P., Vieira A.P., Malva J.O.,Oliveira C.R. Susceptibility of hippocampal neurons to Abeta peptide toxicity is associated with perturbation of Ca2+ homeostasis .Ibid. 2007. 1143. P. 11-21. CrossRef PubMed
  58. Rizzuto R., Brini M., Murgia M.,Pozzan T. Micro-domains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria . Science. 1993. 262. P. 744-747. CrossRef PubMed
  60. Romanenko S.V., Kostyuk E.P., Kostyuk P.G. Specific­ity of gabapentin action in different populations of dor­sal root ganglion neurons of rats with streptozotocin-induced diabetes . Neurophysiology. 2009. 41. P. 119-130. CrossRef  
  61. van der S.M., Di M., V. Endovanilloids. Putative en­dogenous ligands of transient receptor potential vanilloid 1 channels . Eur.J.Biochem. 2004. 271. P. 1827-1834. CrossRef PubMed
  63. Veldhuis W.B., van der S.M., Wadman M.W., van Z.G.,Maccarrone M., Fezza F., Veldink G.A., Vliegenthart J.F., Bar P.R., Nicolay K.,Di M., V. Neuroprotection by the endogenous cannabinoid anandamide and arvanil against in vivo excitotoxicity in the rat: role of vanilloid receptors and lipoxygenases . J.Neurosci. 2003. 23. P. 4127-4133. CrossRef PubMed PubMedCentral
  65. Voets T., Droogmans G., Wissenbach U., Janssens A., Flockerzi V.,Nilius B. The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels . Nature. 2004. 430. P. 748-754. 37. Webster S., Bradt B., Rogers J.,Cooper N. Aggregation state-dependent activation of the classical complement pathway by the amyloid beta peptide . J.Neurochem. 1997. 69. P. 388-398. CrossRef PubMed

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.