Korean J Physiol Pharmacol.  1999 Jun;3(3):305-313.

Effects of Cl- channel blockers on the cardiac ATP-sensitive K+ channel

• Kwak YG

Abstract

To explore whether Cl- channel blockers interact with the ATP-sensitive K+ (KATP) channel, I have examined the effect of two common Cl- channel blockers on the KATP 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 KATP channel activity in a concentration-dependent manner with IC50 of 0.24 and 927 muM, 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 KATP channel openings. In contrast, niflumic acid did not block the pinacidil-induced KATP 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- channel blockers specifically blocks the cardiac KATP channel.

Keyword

DIDS; Niflumic acid; Cl- channel; K ATP channel; Ventricular myocyte

MeSH Terms

2,4-Dinitrophenol
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Adenosine Triphosphate
Animals
Baths
Inhibitory Concentration 50
Kinetics
Muscle Cells
Niflumic Acid
Patch-Clamp Techniques
Rats
2,4-Dinitrophenol
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Adenosine Triphosphate
Niflumic Acid