Effects of Cl- channel blockers on the cardiac ATP-sensitive K+ channel.
- Author:
Yong Geun KWAK
1
Author Information
1. Department of Pharmacology, Chonbuk National University Medical School, Chonju, 560-182 South Korea.
- Publication Type:Original Article
- Keywords:
DIDS;
Niflumic acid;
Cl- channel;
K ATP channel;
Ventricular myocyte
- MeSH:
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
- From:The Korean Journal of Physiology and Pharmacology
1999;3(3):305-313
- CountryRepublic of Korea
- Language:English
-
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.
