BURST KINETICS OF COEXPRESSED KIR6.2 SUR1 CLONES - COMPARISON OF RECOMBINANT WITH NATIVE ATP-SENSITIVE K+ CHANNEL BEHAVIOR/

Co-expression of clones encoding Kir6.2, a K+ inward rectifier, and SU R1, a sulfonylurea receptor, reconstitutes elementary features of ATP- sensitive K+ (K-ATP) channels. However, the precise kinetic properties of Kir6.2/SUR1 clones remain unknown. Herein, intraburst kinetics of Kir6.2/SUR1 channel activity, heterologously co-expressed in COS cells , displayed mean closed times from 0.7 +/- 0.1 to 0.4 +/- 0.03 msec, a nd from 0.4 +/- 0.1 to 2.0 +/- 0.2 msec, and mean open times from 1.9 +/- 0.4 to 4.5 +/- 0.8 msec, and from 12.1 +/- 2.4 to 5.0 +/- 0.2 msec between -100 and -20 mV, and +20 to +80 mV, respectively. Burst durat ion for Kir6.2/SUR1 activity was 17.9 +/- 1.8 msec with 5.6 +/- 1.5 cl osings per burst. Burst kinetics of the Kir6.2/SUR1 activity could be fitted by a four-state kinetic model defining transitions between one open and three closed states with forward and backward rate constants of 1905 +/- 77 and 322 +/- 27 sec(-1) for intraburst, 61.8 +/- 6.6 and 23.9 +/- 5.8 sec(-1) for interburst, 12.4 +/- 6.0 and 13.6 +/- 2.9 se c(-1) for intercluster events, respectively. Intraburst kinetic proper ties of Kir6.2/SUR1 clones were essentially indistinguishable from pan creatic or cardiac K-ATP channel phenotypes, indicating that intraburs t kinetics per se were insufficient to classify recombinant Kir6.2/SUR 1 amongst native K-ATP channels. Yet, burst kinetic behavior of Kir6.2 /SUR1 although similar to pancreatic, was different from that of cardi ac K-ATP channels. Thus, expression of Kir6.2/SUR1 proteins away from the pancreatic microenvironment, confers the burst kinetic identity of pancreatic, but not cardiac K-ATP channels. This study reports the ki netic properties of Kir6.2/SUR1 clones which could serve in the furthe r characterization of novel K-ATP channel clones.