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

Jan Benedikt, Christian J. Malpica-Nieves, Yomarie Rivera, Miguel Méndez-González, Colin G. Nichols, Rüdiger W. Veh, Misty J. Eaton, Serguei N. Skatchkov

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The interest in astrocytes, the silent brain cells that accumulate polyamines (PAs), is growing. PAs exert anti-inflammatory, antioxidant, antidepressant, neuroprotective, and other beneficial effects, including increasing longevity in vivo. Unlike neurons, astrocytes are extensively coupled to others via connexin (Cx) gap junctions (GJs). Although there are striking modulatory effects of PAs on neuronal receptors and channels, PA regulation of the astrocytic GJs is not well understood. We studied GJ-propagation using molecules of different (i) electrical charge, (ii) structure, and (iii) molecular weight. Loading single astrocytes with patch pipettes containing membrane-impermeable dyes, we observed that (i) even small molecules do not easily permeate astrocytic GJs, (ii) the ratio of the charge to weight of these molecules is the key determinant of GJ permeation, (iii) the PA spermine (SPM) induced the propagation of negatively charged molecules via GJs, (iv) while no effects were observed on propagation of macromolecules with net-zero charge. The GJ uncoupler carbenoxolone (CBX) blocked such propagation. Taken together, these findings indicate that SPM is essential for astrocytic GJ communication and selectively facilitates intracellular propagation via GJs for negatively charged molecules through glial syncytium.

Original languageEnglish
Article number1812
JournalBiomolecules
Volume12
Issue number12
DOIs
StatePublished - Dec 2022

Keywords

  • astrocytes
  • connexin
  • glial syncytium
  • polyamines

Fingerprint

Dive into the research topics of 'The Polyamine Spermine Potentiates the Propagation of Negatively Charged Molecules through the Astrocytic Syncytium'. Together they form a unique fingerprint.

Cite this