Effects of Cl<SUP>&#8291;</SUP> Channel Blockers on the Cardiac ATP-sensitive K<SUP>&#8290;</SUP> Channel

Effects of Cl<SUP>&#8291;</SUP> Channel Blockers on the Cardiac ATP-sensitive K<SUP>&#8290;</SUP> Channel

<P> To explore whether Cl<SUP>&#8291;</SUP> channel blockers interact with the ATP-sensitive K<SUP>&#8290; </SUP>(K<SUB>ATP</SUB>) channel, I have examined the effect of two common Cl<SUP>&#8291;</SUP> channel blockers on the K<SUB>ATP</SUB> channel activity in isolated rat ventricular myocytes using patch clamp techniques. In inside-out patches, 4,4 -diisothio-cyanatostilbene- 2,2 -disulfonic acid (DIDS) and niflumic acid applied to bath solution inhibited the K<SUB>ATP</SUB> channel activity in a concentration-dependent manner with IC<SUB>50</SUB> of 0.24 and 927μM, respectively. The inhibitory action of DIDS was irreversible whereas that of niflumic acid was reversible. Furthermore, DIDS-induced block was not recovered despite exposure to ATP (1 mM). In cell-attached and inside-out patches, DIDS blocked the pinacidil- or 2,4-dinitrophenol (DNP)-induced K<SUB>ATP</SUB> channel openings. In contrast, niflumic acid did not block the pinacidil-induced K<SUB>ATP</SUB> channel openings in inside-out patches, but inhibited it in cell-attached patches. DIDS and niflumic acid produced additional block in the presence of ATP and did not affect current-voltage relationship and channel kinetics. All these results indicate that DIDS among Cl<SUP>&#8291;</SUP> channel blockers specifically blocks the cardiac K<SUB>ATP</SUB> channel.