TYROSINE KINASE-DEPENDENT SUPPRESSION OF A POTASSIUM CHANNEL BY THE G-PROTEIN-COUPLED M1-MUSCARINIC ACETYLCHOLINE-RECEPTOR

Neurotransmitter receptors alter membrane excitability and synaptic ef ficacy by generating intracellular signals that ultimately change the properties of ion channels. Through expression studies in Xenopus oocy tes and mammalian cells, we found that the G protein-coupled m1 muscar inic acetylcholine receptor potently suppresses a cloned delayed recti fier K+ channel through a pathway involving phospholipase C activation and direct tyrosine phosphorylation of the K+ channel. Furthermore, a nalysis of neuroblastoma cells revealed that a similar tyrosine kinase -dependent pathway links endogenous G protein-coupled receptors to sup pression of the native RAK channel. These results suggest a novel mech anism by which neurotransmitters and hormones may regulate a specific type of K+ channel that is widely expressed in the mammalian brain and heart.