␣7 nicotinic acetylcholine receptors (nAChRs) modulate network activity in the CNS. Thus, functional regulation of ␣7 nAChRs could influence the flow of information through various brain nuclei. It is hypothesized here that these receptors are amenable to modulation by tyrosine phosphorylation. In both Xenopus oocytes and rat hippocampal interneurons, brief exposure to a broad-spectrum protein tyrosine kinase inhibitor, genistein, specifically and reversibly potentiated ␣7 nAChR-mediated responses, whereas a protein tyrosine phosphatase inhibitor, pervanadate, caused depression. Potentiation was associated with an increased expression of surface ␣7 subunits and was not accompanied by detectable changes in receptor open probability, implying that the increased function results from an increased number of ␣7 nAChRs. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated exocytosis was shown to be a plausible mechanism for the rapid delivery of additional ␣7 nAChRs to the plasma membrane. Direct phosphorylation/ dephosphorylation of ␣7 subunits was unlikely because mutation of all three cytoplasmic tyrosine residues did not prevent the genisteinmediated facilitation. Overall, these data are consistent with the hypothesis that the number of functional cell surface ␣7 nAChRs is controlled indirectly via processes involving tyrosine phosphorylation.
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Neurotransmitter transporters belong to the superfamily of solute carrier. Transporters regulate transmitter levels in the extracellular space and in transmitter‐containing vesiclesby controlling the movement of transmitter between various intracellular andextracellular compartments in brain. This function is achieved in part by coupling the movement of transmitter against its concentration gradient to the movement of associated ions down their electrochemical gradients. Disruption of the normal transport process isassociated with a variety of brain disorders including Alzheimer's disease, depression, epilepsy, Parkinson's disease, stroke, and substance abuse. Moreover, some transportersin this gene family are primary targets of potent psychoactive drugs such as cocaine, amphetamine, and antidepressants. Neurons and glia have multiple mechanisms by which they control transporter expression and function on a variety of time scales. This regulation is not only important for understanding the role of transporters in physiological and pathological processes, but may provide mechanistic targets for therapeutics aimed at disorders related to abnormal transmitter levels.
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