A Point Mutation of the α 2 -Adrenoceptor that Blocks Coupling to Potassium but not Calcium Currents

• DOI: 10.1126/science.1354394
• Publication Date: 2006-10-05T23:03:06Z
• Authors: Annmarie Surprenant; Debra A. Horstman; Hamid Akbarali; Lee E. Limbird
• Keywords: 0301 basic medicine; Aspartic Acid; Potassium Channels; Receptors, Adrenergic, alpha; Transfection; Clonidine; Recombinant Proteins; Cell Line; Membrane Potentials; Receptors, Neurotransmitter; 03 medical and health sciences; GTP-Binding Proteins; Brimonidine Tartrate; Quinoxalines; Mutagenesis, Site-Directed; Animals; Calcium Channels; Receptors, Somatostatin; Asparagine; Somatostatin; Adrenergic alpha-Agonists

The α 2A -adrenergic receptor (adrenoceptor) was stably expressed in AtT20 mouse pituitary tumor cells; adrenoceptor agonists inhibited adenylyl cyclase, inhibited voltage-dependent calcium currents, and increased inwardly rectifying potassium currents. An aspartic acid residue (Asp 79 ) highly conserved among guanine nucleotide-binding protein (G protein)-coupled receptors was mutated to asparagine; in cells transfected with the mutant α 2 -receptor, agonists inhibited adenylyl cyclase and calcium currents but did not increase potassium currents. Because distinct G proteins appear to couple adrenoceptors to potassium and calcium currents, the present findings suggest that the mutant α 2 -adrenoceptor cannot achieve the conformation necessary to activate G proteins that mediate potassium channel activation.