Astrocytic Gap Junctions Remain Open During Ischemic Conditions

Overview

Journal J Neurosci

Specialty Neurology

Date 1998 Apr 16

PMID 9502812

Citations 70

Authors

M L Cotrina

J Kang

J H Lin

E Bueno

T W Hansen

L He

Y Liu

M Nedergaard

Affiliations

Soon will be listed here.

Abstract

Gap junctions are highly conductive channels that allow the direct transfer of intracellular messengers such as Ca2+ and inositol triphosphate (IP3) between interconnected cells. In brain, astrocytes are coupled extensively by gap junctions. We found here that gap junctions among astrocytes in acutely prepared brain slices as well as in culture remained open during ischemic conditions. Uncoupling first occurred after the terminal loss of plasma membrane integrity. Gap junctions therefore may link ischemic astrocytes in an evolving infarct with the surroundings. The free exchange of intracellular messengers between dying and potentially viable astrocytes might contribute to secondary expansion of ischemic lesions.

Citing Articles

Calcium Role in Gap Junction Channel Gating: Direct Electrostatic or Calmodulin-Mediated?.

Peracchia C Int J Mol Sci. 2024; 25(18).

PMID: 39337278 PMC: 11432632. DOI: 10.3390/ijms25189789.

Gap Junction Channel Regulation: A Tale of Two Gates-Voltage Sensitivity of the Chemical Gate and Chemical Sensitivity of the Fast Voltage Gate.

Peracchia C Int J Mol Sci. 2024; 25(2).

PMID: 38256055 PMC: 10815820. DOI: 10.3390/ijms25020982.

Targeting Cx43 to Reduce the Severity of Pressure Ulcer Progression.

Kwek M, Thangaveloo M, Madden L, Phillips A, Becker D Cells. 2023; 12(24).

PMID: 38132176 PMC: 10741864. DOI: 10.3390/cells12242856.

Ca-dependent rapid uncoupling of astrocytes upon brief metabolic stress.

Eitelmann S, Everaerts K, Petersilie L, Rose C, Stephan J Front Cell Neurosci. 2023; 17:1151608.

PMID: 37886111 PMC: 10598858. DOI: 10.3389/fncel.2023.1151608.

The Polyamine Spermine Potentiates the Propagation of Negatively Charged Molecules through the Astrocytic Syncytium.

Benedikt J, Malpica-Nieves C, Rivera Y, Mendez-Gonzalez M, Nichols C, Veh R Biomolecules. 2022; 12(12).

PMID: 36551240 PMC: 9775384. DOI: 10.3390/biom12121812.

References

Hossmann K . Viability thresholds and the penumbra of focal ischemia. Ann Neurol. 1994; 36(4):557-65. DOI: 10.1002/ana.410360404. View

Nedergaard M, Desai S, Pulsinelli W . Dicarboxy-dichlorofluorescein: a new fluorescent probe for measuring acidic intracellular pH. Anal Biochem. 1990; 187(1):109-14. DOI: 10.1016/0003-2697(90)90425-9. View

Dietrich W, Busto R, Globus M, Ginsberg M . Brain damage and temperature: cellular and molecular mechanisms. Adv Neurol. 1996; 71:177-94; discussion 194-7. View

Siesjo B, Zhao Q, Pahlmark K, Siesjo P, Katsura K, Folbergrova J . Glutamate, calcium, and free radicals as mediators of ischemic brain damage. Ann Thorac Surg. 1995; 59(5):1316-20. DOI: 10.1016/0003-4975(95)00077-x. View

Iijima T, Mies G, Hossmann K . Repeated negative DC deflections in rat cortex following middle cerebral artery occlusion are abolished by MK-801: effect on volume of ischemic injury. J Cereb Blood Flow Metab. 1992; 12(5):727-33. DOI: 10.1038/jcbfm.1992.103. View

Astrup J, Siesjo B, Symon L . Thresholds in cerebral ischemia - the ischemic penumbra. Stroke. 1981; 12(6):723-5. DOI: 10.1161/01.str.12.6.723. View

Tymianski M, Wallace M, Spigelman I, Uno M, Carlen P, Tator C . Cell-permeant Ca2+ chelators reduce early excitotoxic and ischemic neuronal injury in vitro and in vivo. Neuron. 1993; 11(2):221-35. DOI: 10.1016/0896-6273(93)90180-y. View

Siesjo B . Pathophysiology and treatment of focal cerebral ischemia. Part I: Pathophysiology. J Neurosurg. 1992; 77(2):169-84. DOI: 10.3171/jns.1992.77.2.0169. View

McLarnon J, Wong J, Sawyer D, Baimbridge K . The actions of intermediate and long-chain n-alkanols on unitary NMDA currents in hippocampal neurons. Can J Physiol Pharmacol. 1991; 69(10):1422-7. DOI: 10.1139/y91-213. View

10.

Wolszon L, Rehder V, Kater S, Macagno E . Calcium wave fronts that cross gap junctions may signal neuronal death during development. J Neurosci. 1994; 14(6):3437-48. PMC: 6576958. View

11.

Nedergaard M . Intracellular Ca2+ transients evoked by lactic acid in cultured mammalian neurons. Am J Physiol. 1995; 268(2 Pt 2):R506-13. DOI: 10.1152/ajpregu.1995.268.2.R506. View

12.

Lattanzio Jr F . The effects of pH and temperature on fluorescent calcium indicators as determined with Chelex-100 and EDTA buffer systems. Biochem Biophys Res Commun. 1990; 171(1):102-8. DOI: 10.1016/0006-291x(90)91362-v. View

13.

Astrup J, Symon L, Branston N, Lassen N . Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke. 1977; 8(1):51-7. DOI: 10.1161/01.str.8.1.51. View

14.

Dermietzel R, Hertberg E, Kessler J, Spray D . Gap junctions between cultured astrocytes: immunocytochemical, molecular, and electrophysiological analysis. J Neurosci. 1991; 11(5):1421-32. PMC: 6575331. View

15.

Giaume C, Fromaget C, el Aoumari A, Cordier J, Glowinski J, Gros D . Gap junctions in cultured astrocytes: single-channel currents and characterization of channel-forming protein. Neuron. 1991; 6(1):133-43. DOI: 10.1016/0896-6273(91)90128-m. View

16.

Dermietzel R, Spray D . Gap junctions in the brain: where, what type, how many and why?. Trends Neurosci. 1993; 16(5):186-92. DOI: 10.1016/0166-2236(93)90151-b. View

17.

Pappas C, Rioult M, Ransom B . Octanol, a gap junction uncoupling agent, changes intracellular [H+] in rat astrocytes. Glia. 1996; 16(1):7-15. DOI: 10.1002/(SICI)1098-1136(199601)16:1<7::AID-GLIA2>3.0.CO;2-2. View

18.

Pellegrini-Giampietro D, CHERICI G, Alesiani M, Carla V, Moroni F . Excitatory amino acid release and free radical formation may cooperate in the genesis of ischemia-induced neuronal damage. J Neurosci. 1990; 10(3):1035-41. PMC: 6570140. View

19.

Bennett M, Barrio L, Bargiello T, Spray D, Hertzberg E, Saez J . Gap junctions: new tools, new answers, new questions. Neuron. 1991; 6(3):305-20. DOI: 10.1016/0896-6273(91)90241-q. View

20.

Nedergaard M . Direct signaling from astrocytes to neurons in cultures of mammalian brain cells. Science. 1994; 263(5154):1768-71. DOI: 10.1126/science.8134839. View