Listening to Neurotransmitter Transporters

However, the conducting properties of transporters go well beyond this simple picture (Sonders and Amara, Division of Biology California Institute of Technology 1996). For example, the 5-HT transporter is not electro-genic; yet it displays at least four distinct conducting Pasadena, California 91125 states (Mager et al., 1994). Three of these states are permeable to Na ϩ ions, and the other to protons; and recent results show that at least two of the Na ϩ conduc-Our title recalls Listening to Prozac, the bestseller describing clinical case histories of patients who have been tances arise from unitary events that resemble single channel openings, with conductances of a few pS and aided by fluoxetine (Kramer, 1993). Fluoxetine typifies a new class of antidepressants called serotonin-selective open durations of a few ms (Lin et al., 1996). If one assumes that these events arise uniformly from all trans-reuptake inhibitors (SSRIs). The fraction of adults who take SSRIs may be exceeded only by the fraction of porters in the membrane, then the open probability is about 10 Ϫ6 ; and an individual transporter produces an children diagnosed with attention-deficit disorder or attention deficit-hyperactivity disorder who benefit from opening only once per 350–700 transport cycles. One of these channel-based conducting states occurs in the methylphenidate (Ritalin) or other drugs thought to act on monoamine transporters either by blocking uptake presence of substrate, and one " leakage " state in its absence. Evidently channel events are not an obligate or by enhancing release. Modern concepts of therapeutics would imply that part of each transport cycle. However, we do not know whether channel events arise from a subpopulation of such success stories arise because of highly specific actions on one subtype of target molecule. Yet the transporters with abnormal properties. Channel-like unitary events are confined neither to known neurotransmitter transporter families are much smaller than the superfamilies that comprise 7-helix re-5-HT transporters nor to oocyte expression systems and, in the case of glutamate transporters, also occur ceptors and ligand-gated channels. There are, for example , at least fourteen known serotonin receptor genes, in native cells. All cloned mammalian monoamine transporters also display " excess transport-associated cur-but only one known serotonin transporter gene, and another one apiece for dopamine and noradrenaline/ rent, " which may be explained by the channel-like events. When measurements of macroscopic current adrenaline (the last is relatively nonspecific). Because the unique serotonin transporter is widely expressed, …