Faculty Collaboration Database

Accelerated inactivation of cardiac L-type calcium channels triggered by anaesthetic-induced preconditioning. Br J Pharmacol 2009 Feb;156(3):432-43

Date

01/22/2009

Pubmed ID

19154423

Pubmed Central ID

PMC2697672

DOI

10.1111/j.1476-5381.2008.00026.x

Scopus ID

2-s2.0-65449143981 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

BACKGROUND AND PURPOSE: Cardioprotection against ischaemia by anaesthetic-induced preconditioning (APC) is well established. However, the mechanism underlying Ca(2+) overload attenuation by APC is unknown. The effects of APC by isoflurane on the cardiac L-type Ca channel were investigated.

EXPERIMENTAL APPROACH: In a model of in vivo APC, Wistar rats were exposed to isoflurane (1.4%), delivered via a vaporizer in an enclosure, prior to thoracotomy. The Dahl S rats were similarly preconditioned to determine strain-dependent effects. Whole-cell patch clamp using cardiac ventricular myocytes was used to determine the L-type Ca(2+) current (I(Ca,L)) characteristics and calmodulin (CaM) levels were determined by Western blot analysis. Cytosolic Ca(2+) levels were monitored using fluo-4-AM. Action potential (AP) simulations examined the effects of APC.

KEY RESULTS: In Wistar rats, APC significantly accelerated I(Ca,L) inactivation kinetics. This was abolished when external Ca(2+) was replaced with Ba(2+), suggesting that Ca(2+)-dependent inactivation of I(Ca,L) was modulated by APC. Expression levels of CaM, a determinant of I(Ca,L) inactivation, were not affected. Attenuation of cytosolic Ca(2+) accumulation following oxidative stress was observed in the APC group. Simulations showed that the accelerated inactivation of I(Ca,L) resulted in a shortening of the AP duration. The Dahl S rat strain was resistant to APC and changes in I(Ca,L) inactivation were not observed in cardiomyocytes prepared from these rats.

CONCLUSIONS AND IMPLICATIONS: APC triggered persistent changes in the inactivation of cardiac L-type Ca channels. This can potentially lead to a reduction in Ca(2+) influx and attenuation of Ca(2+) overload during ischaemia/reperfusion.

Author List

Tampo A, Hogan CS, Sedlic F, Bosnjak ZJ, Kwok WM

Authors

Zeljko Bosnjak PhD, MS Emeritus Professor in the Medicine department at Medical College of Wisconsin
Wai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anesthetics, Inhalation
Animals
Barium
Blotting, Western
Calcium
Calcium Channels, L-Type
Cell Survival
Cells, Cultured
Cytosol
Heart Ventricles
Ion Channel Gating
Ischemic Preconditioning, Myocardial
Isoflurane
Male
Myocytes, Cardiac
Oxidative Stress
Patch-Clamp Techniques
Rats
Rats, Inbred Dahl
Rats, Wistar