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

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.

Advances in the Electrophysiological Recordings of Long-Term Potentiation

“…Molecular communication can travel a long distance. Neurons are divided from each other by the aquatic cleft of synapses and thus cannot interact directly with each other except through chemical communication [ 127 ]. However, astrocytes communicate extensively via large pores known as gap junctions, which may propagate molecular signaling to a long distance [ 128 ].…”

“…However, astrocytes communicate extensively via large pores known as gap junctions, which may propagate molecular signaling to a long distance [ 128 ]. Moreover, this communication is enforced by polyamine spermine [ 127 , 128 ]. Polyamines, such as putrescine and spermine, are also gliotransmitters [ 118 ].…”

Spermidine Synthase Localization in Retinal Layers: Early Age Changes

“…In the retina, PAs regulate the glial Kir4.1 channels in Müller cells [ 28 , 45 , 57 , 58 , 59 , 60 ] and can permeate Kir4.1 [ 59 ]. PAs open glial Cx43 channels [ 61 , 62 , 63 ] that are expressed in Müller retinal glial cells [ 63 ] and rescue Cx43 channels from hydrogen and calcium block. In addition, PAs may permeate Cx43 [ 61 , 62 , 63 , 64 , 65 ] and open a traffic pathway for other molecules [ 61 , 62 , 63 , 64 , 65 ].…”

“…PAs open glial Cx43 channels [ 61 , 62 , 63 ] that are expressed in Müller retinal glial cells [ 63 ] and rescue Cx43 channels from hydrogen and calcium block. In addition, PAs may permeate Cx43 [ 61 , 62 , 63 , 64 , 65 ] and open a traffic pathway for other molecules [ 61 , 62 , 63 , 64 , 65 ]. Therefore, Müller cells, astrocytes, and the glial–neuronal communication in the retina need PAs [ 45 , 62 , 63 ].…”

“…In addition, PAs may permeate Cx43 [ 61 , 62 , 63 , 64 , 65 ] and open a traffic pathway for other molecules [ 61 , 62 , 63 , 64 , 65 ]. Therefore, Müller cells, astrocytes, and the glial–neuronal communication in the retina need PAs [ 45 , 62 , 63 ]. PAs are extremely effective in various CNS functions [ 4 , 50 , 56 , 66 , 67 ], and SPD has been found to ameliorate or suppress oxidative stress in an animal model of optic nerve multiple sclerosis [ 68 ].…”