A POINT MUTATION OF THE ALPHA-2-ADRENOCEPTOR THAT BLOCKS COUPLING TO POTASSIUM BUT NOT CALCIUM CURRENTS

The alpha-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 (Asp79) highly conserved among guanine nucleotide-binding protein (G protein)-coupled receptors was mutated to asparagine; in cells transfected with the mutant alpha-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 alpha-2-adrenoceptor cannot achieve the conformation necessary to activate G proteins that mediate potassium channel activation.