Iron modulates norepinephrine effect on astrocytes

Abstract

Aims: Astrocyte position between synapses and blood vessels allows them to ful l crucial functions such as regulation of synaptic activity and potassium bu ering. Well positioned in the close vicinity of synaptic cleft astrocytes are considered to be a direct target of norepinephrine (NE). Synaptic activity and neurotransmitter actions can be in uenced by extracellular iron. Here we investigated whether iron interacts with NE and if this interaction can modulate astrocyte response to NE. Methods: To investigate the interaction between iron and norepinephrine we used spectrophotometry approach. Iron e ect on astrocyte response to NE was examined by the whole-cell patch-clamp technique. Membrane currents were recorded from cultured cortical astrocytes prepared from WT rats. Results: Using spectrophotometry we observed that iron interacts with NE which leads to the formation of a stable complex in the 1:1 stoichiometry. We also found that iron bound to NE completely blocks NE-induced increase of large-conductance calcium sensitive potassium current in astrocytes. Conclusions: Astrocyte response to NE is modi ed when this neurotransmitter forms a complex with iron. This implies that NE binding to astrocytic noradrenergic receptors may be prevented by iron. Our ndings point toward compromised astrocyte functions related to the potassium bu ering when NE action is modi ed by iron.