Handbook of experimental pharmacology
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Handb Exp Pharmacol · Jan 2006
ReviewAcute regulation of sodium-dependent glutamate transporters: a focus on constitutive and regulated trafficking.
The acidic amino acid glutamate activates a family of ligand-gated ion channels to mediate depolarization that can be as short-lived as a few milliseconds and activates a family of G protein-coupled receptors that couple to both ion channels and other second messenger pathways. Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system and is required for essentially all motor, sensory, and cognitive functions. In addition, glutamate-mediated signaling is required for development and the synaptic plasticity thought to underlie memory formation and retrieval. ⋯ The glutamate transporters found in forebrain are regulated by redistributing the proteins to or from the plasma membrane; the signals involved and the net effects on transporter activity are being defined. In addition, there is evidence to suggest that the intrinsic activity of these transporters is also regulated by mechanisms that are independent of transporter redistribution; less is known about these events. As this field progresses, it should be possible to determine how this regulation affects physiologic and pathologic events in the CNS.
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Drugs that suppress beta-adrenergic signaling by competitively inhibiting agonist binding to beta-adrenergic receptors ("beta-blockers") have important antiarrhythmic properties. They differ from most other antiarrhythmic agents by not directly modifying ion channel function; rather, they prevent the arrhythmia-promoting actions of beta-adrenergic stimulation. beta-Blockers are particularly useful in preventing sudden death due to ventricular tachyarrhythmias associated with acute myocardial ischemia, congenital long QT syndrome, and congestive heart failure. They are also quite valuable in controlling the ventricular rate in patients with atrial fibrillation. This chapter reviews the properties of beta-adrenoceptor signaling, the basic mechanisms of cardiac arrhythmias on which beta-blockers act, the ion channel mediators of beta-adrenergic responses, the evidence for clinical antiarrhythmic indications for beta-blocker therapy and the specific pharmacodynamic and pharmacokinetic properties of beta-blockers that differentiate the various agents of this class.