© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Swelling-activated chloride current is activated in guinea pig cardiomyocytes from endotoxic shock
aDivision of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan
bGraduate Institute of Medical Science, Taipei Medical University, Taipei, Taiwan
cDepartment of Anesthesiology, Chang-Gung Memorial Hospital-Kaohsiung, Taipei, Taiwan
* Corresponding author. Division of Cardiology, Taipei Veterans General Hospital 201, Sec 2, Shih-Pai Road, Taipei 112, Taiwan. Tel.: +886-2-2875-7602; fax: +886-2-2874-5422. Email address: cechiang{at}vghtpe.gov.tw
Objective: Myocardial swelling occurs during endotoxic shock. The hypothesis that swelling-activated Cl– current (ICl,swell) activates during endotoxic shock was tested. Methods: Endotoxic shock was induced by intravenous lipopolysaccharides (10 mg/kg) in guinea pigs. The effects of ICl,swell blockers on the cardiac action potentials in papillary muscles and on the ICl,swell in single ventricular myocytes were tested. Results: Action potential duration (APD) at 90% of repolarization (APD90) was significantly shortened after 5-h endotoxic shock in guinea pig papillary muscles. ICl,swell blockers, 9-anthracene carboxylic acid (9-AC) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), dose-dependently prolonged the shortened APD90. Inducible nitric oxide synthase (iNOS) inhibitors, L-N6-(1-iminoethyl) lysine (L-NIL) and N-[[3-(aminomethyl)phenyl]methyl]-ethanimidamide (1400 W), also prolonged the APD90. Protein kinase C (PKC) activators, 4β-phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-didecanoate (PDD), also prolonged the APD. The addition of glibenclamide (an ATP-sensitive K+ channel blocker) on top of these ICl,swell blockers hastened the recovery of APD90 compared to the use of ICl,swell blockers alone. Whole-cell voltage-clamp study in single ventricular myocytes from endotoxic shock heart disclosed activation of a DIDS- and 9-AC-sensitive current. These currents displayed outward rectification with reversal potentials similar to the calculated Nernst potential for Cl–. The reversal potentials tracked the ECl closely when the Cl– gradient was changed, suggesting that Cl– was the major charged carrier. Conclusions: We have shown for the first time that ICl,swell activates in guinea pig heart in endotoxic shock. The change in this membrane current, together with the activation of ATP-sensitive K+ current, contributes to the electrophysiological derangement in endotoxic shock.
KEYWORDS Guinea pigs; Ion channels; Septic shock
Time for primary review 19 days
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