Reciprocal modulation of ATP-sensitive K+ channel activity in rat ventricular myocytes by phosphorylation of tyrosine and serine threonine residues

The modulation of ATP-sensitive K+ channel (K-ATP) activity by specific phosphorylation or dephosphorylation of tyrosine and serine/threonine residues was examined in rat ventricular myocytes using the inside-out patch configuration of the patch clamp technique. The run-down process was suppressed by okadaic acid but accelerated by sodium orthovanadate. After run-down of the channels, the ATP-induced reactivation was blocked by H-7, but enhanced by genistein. The channel activity was decreased by protein phosphatase 2A. However, the activity of partially run-down channels was increased by protein tyrosine phosphatase 1B. Our results suggest that K-ATP channel activity can be inhibited by phosphorylation of tyrosine residues and stimulated by phosphorylation of serine/threonine residues.