Amiloride derivatives are potent blockers of KATP channels

C. Bollensdorff, T. Zimmer, K. Benndorf

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

In cardiomyocytes sarcolemmal KATP channels open massively when the cytosolic [ATP] drops into the range of tens of micromolar, as during acute ischemia. The diuretic drug amiloride and related derivatives are well established as drugs blocking the Na+/H+- and the Na+/Ca2+-exchange, protecting the ischemic heart. Herein, the blocking action of amiloride and its derivatives 2',4'-dichlorobenzamil (DCB) and 5-(N-ethyl-N-isopropyl)amiloride (EIPA) on KATP channels was tested. In inside-out patches of mouse cardiac myocytes, amiloride, DCB, and EIPA reversibly blocked the KATP channels with the IC50 values 102, 1.80, and 2.14 μmol/l (-80 mV), respectively. Similar IC50 values were obtained in recombinant channels when coexpressing the KIR6.2 subunit with one of the sulfonylurea receptors SUR1 and SUR2A. All three drugs also blocked currents generated by the C-terminus deletion mutant KIR6.2Δ26 in the absence of SUR. Amiloride blocked outward currents more effectively than inward currents whereas the block by DCB and EIPA was voltage independent. In cardiomyocytes, also whole-cell IKATP was blocked by the three drugs. In conclusion, amiloride, EIPA, and DCB block the pore-forming KIR6.2 subunit of cardiac KATP channels with higher potency than the Na+/H+- and the Na+/Ca2+-exchange, precluding a specific block of the exchanges under ischemic conditions.

Original languageEnglish
Pages (from-to)351-358
Number of pages8
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume364
Issue number4
DOIs
Publication statusPublished - 16 Oct 2001
Externally publishedYes

Fingerprint

KATP Channels
Amiloride
Cardiac Myocytes
Pharmaceutical Preparations
Inhibitory Concentration 50
Sulfonylurea Receptors
Diuretics
Ischemia
Adenosine Triphosphate

Keywords

  • ATP
  • Ischemia
  • K currents
  • Na/Ca-exchange
  • Na/H-exchange

ASJC Scopus subject areas

  • Pharmacology

Cite this

Amiloride derivatives are potent blockers of KATP channels. / Bollensdorff, C.; Zimmer, T.; Benndorf, K.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 364, No. 4, 16.10.2001, p. 351-358.

Research output: Contribution to journalArticle

Bollensdorff, C. ; Zimmer, T. ; Benndorf, K. / Amiloride derivatives are potent blockers of KATP channels. In: Naunyn-Schmiedeberg's Archives of Pharmacology. 2001 ; Vol. 364, No. 4. pp. 351-358.
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