Abstract
It has been proposed that ischemic preconditioning involves the regulation of ATP-sensitive potassium (K(ATP)) channels. The evidence is based largely on the ability of certain K(ATP) channel modulators to modify the protection in the various models of preconditioning. This study has investigated how two K(ATP) channel openers, pinacidil and nicorandil, affect both membrane currents and viability in isolated and ischemic rabbit cardiomyocytes. We used the whole-cell recording technique and in separate experiments viability was assessed by exposure to these drugs during ischemia. Pinacidil (50 micromol/l) increased K(ATP) current approximately four-fold in isolated cardiomyocytes. This increase reversed rapidly after treatment with the K(ATP) channel blocker glibenclamide (200 nmol/l). After simulated ischemia, pinacidil protected cardiomyocytes (the area under cell-death curve was 29.5 +/- 1.1% x h) which was significantly less than that in control (46.9 +/- 2.0% x h). The protection from pinacidil could be completely eliminated by pretreatment with 10 microM glibenclamide (46.9 +/- 2.0% x h). In contrast, nicorandil (1 mmol/l), which opens K(ATP) channels in some tissues, caused no detectable effect on the K(ATP) current. Simi...Continue Reading
Citations
May 24, 2005·Journal of Molecular and Cellular Cardiology·Peter J Hanley, Jürgen Daut
Mar 14, 2002·European Journal of Pharmacology·Biswadeep DasK Sudhakar Karanth
Aug 10, 1999·European Journal of Pharmacology·T TangA K Ho
Jul 1, 1998·Progress in Cardiovascular Diseases·K Przyklenk, R A Kloner
May 5, 2001·Pharmacology & Therapeutics·C NapoliG Cirino
Feb 17, 2000·Journal of the American College of Cardiology·T SatoE Marbán
May 14, 2003·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Biswadeep Das, Chayna Sarkar
Aug 17, 1999·Current Opinion in Cardiology·E R SchwarzR A Kloner
Feb 10, 1998·Journal of Cardiovascular Pharmacology·J ImagawaD M Yellon
Aug 13, 1999·Journal of Cardiovascular Pharmacology·P S FischbachB R Lucchesi
Feb 24, 2001·Free Radical Research·A M HennigeH P Ammon
Jul 29, 1998·The Journal of Physiology·V A LositoP H Backx
Nov 21, 2009·European Journal of Pharmacology·Diethart SchmidThomas Moeslinger
Jul 21, 2007·The Medical Clinics of North America·Allen P Burke, Renu Virmani
Apr 10, 2003·British Journal of Pharmacology·Efstathios K IliodromitisDimitrios Th Kremastinos
Jun 21, 2005·Life Sciences·Biswadeep Das, Chayna Sarkar
Jun 26, 1998·Circulation·Y LiuE Marban
Jan 13, 2009·Physiological Measurement·J K Y LawM Chan
Apr 13, 1999·The American Journal of Physiology·C P BainesJ M Downey
Jun 11, 2017·The Biochemical Journal·Charles Owen SmithPaul S Brookes
Jun 28, 2019·Scientific Reports·Yuejin WuMark E Anderson