ATP-DEPENDENT CLOSURE AND REACTIVATION OF INWARD RECTIFIER K-CELLS( CHANNELS IN ENDOTHELIAL)

This report presents the results of a patch-clamp study examining the role of intracellular ATP in the regulation of endothelial inward rect ifier K+ channels. Administration of ATP to the cytosolic surface of i nside-out patches reversibly activated the K+ channel within seconds. ATP (1 mM) increased the mean open probability by a factor of 3.5, pri marily by increasing the number of openings. Administration of the non hydrolyzable ATP analogue ATP-gamma-S failed to modulate channel activ ity. Inhibition of ATP synthesis by administration of cyanide plus iod oacetate resulted in channel closure within 1 to 6 minutes. In experim ents in which ATP was coadministered with the metabolic blockers, the channel activity continued unchanged for up to 30 minutes, but when AT P was removed, the activity rapidly decayed. We propose that normal fu nctioning of the inward rectifier K+ channel is ATP dependent. Phospho rylation of the channel molecule is probably essential for maintaining activity.