A POSSIBILITY THAT THE ATP-SENSITIVE POTASSIUM CHANNEL IN CORONARY-ARTERY HAS A HIGH-AFFINITY INTERNAL BINDING-SITE FOR TETRAALKYLAMMONIUM

The functionally responsible sites for the blocking action of tetraalk ylammonium ions (TAAs) in ATP-sensitive K+ (K-ATP) channels opened by levcromakalim were estimated in canine coronary artery. Tetraethylammo nium (TEA) and tetrabutylammonium (TBA) inhibited the levcromakalim-in duced relaxation in a noncompetitive manner. Analyses of the noncompet itive antagonism revealed that the binding constant of TBA was about 9 00 times lower than that of TEA, although the reported affinity of TBA for the internal binding site in various K+ channels was only 10 time s higher than that of TEA. TBA is much more lipid-soluble and permeabl e through membranes than TEA. Thus, TBA blocks K-ATP channels by bindi ng to a possible high-affinity internal site for TAAs, whereas TEA see ms to bind to the external site.