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 specifi c phosphorylation or dephosphorylation of tyrosine and serine/threonin e residues was examined in rat ventricular myocytes using the inside-o ut patch configuration of the patch clamp technique. The run-down proc ess was suppressed by okadaic acid but accelerated by sodium orthovana date. After run-down of the channels, the ATP-induced reactivation was blocked by H-7, but enhanced by genistein. The channel activity was d ecreased by protein phosphatase 2A. However, the activity of partially run-down channels was increased by protein tyrosine phosphatase 1B. O ur results suggest that K-ATP channel activity can be inhibited by pho sphorylation of tyrosine residues and stimulated by phosphorylation of serine/threonine residues.