Bestrophin-1 (BEST1) is a ~67 kDa protein. Ligand-gated anion channel that allows the movement of anions across cell membranes when activated by calcium (Ca2+). Allows the movement of chloride and hydrogencarbonate. Found in a partially open conformation leading to significantly smaller chloride movement. Upon F2R/PAR-1 activation, the sequestered calcium is released into the cytosol of astrocytes, leading to the (Ca2+)-dependent release of L-glutamate into the synaptic cleft that targets the neuronal postsynaptic GRIN2A/NMDAR receptor resulting in the synaptic plasticity regulation. Upon activation of the norepinephrine-alpha-1 adrenergic receptor signaling pathway, transports as well D-serine than L-glutamate in a (Ca2+)-dependent manner, leading to activation of adjacent NMDAR receptors and therefore regulates the heterosynaptic long-term depression and metaplasticity during initial memory acquisition. 1. Sun, H. et al. (2002) Proceedings of the National Academy of Sciences of the United States of America 99, 4008-13. PMID: 119044452. Tsunenari, T. et al. (2003) The Journal of biological chemistry 278, 41114-25. PMID: 129076793. Burgess, R. et al. (2008) American journal of human genetics 82, 19-31. PMID: 181798814. Qu, Z. et al. (2008) American journal of physiology. Cell physiology 294, C1371-7. PMID: 184009855. Davidson, AE. et al. (2009) American journal of human genetics 85, 581-92. PMID: 198532386. Davidson, AE. et al. (2011) Investigative ophthalmology & visual science 52, 3730-6. PMID: 213306667. Johnson, AA. et al. (2015) Investigative ophthalmology & visual science 56, 4619-30. PMID: 262005028. Lee, CS. et al. (2015) Investigative ophthalmology & visual science 56, 8141-50. PMID: 267204669. Owji, AP. et al. (2022) Nature communications 13, 3836. PMID: 35789156 | 
