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- Title
CREATINE KINASE INHIBITOR IODOACETAMIDE ANTAGONIZES CALCIUM-STIMULATED INOTROPY IN CARDIOMYOCYTES.
- Authors
Ren, Jun; Davidoff, Amy J; Ingwall, Joanne S
- Abstract
1. Inhibition of creatine kinase is known to suppress cardiac contractile reserve in intact hearts, although the underlying mechanism has not been elucidated. 2. The present study was designed to examine whether cardiac depression induced by creatine kinase inhibition was due to action at the level of the essential contractile element, namely cardiomyocytes. Adult rat cardiomyocytes were perfused with the creatine kinase inhibitor iodoacetamide (90 µmol/L) for 90 min. Mechanical and intracellular Ca2+ properties were evaluated using edge-detection and fluorescence microscopy, respectively. Myocytes were superfused with normal (1.3 mmol/L) or high (3.3 mmol/L) extracellular Ca2+ contractile buffer. Mechanical function was examined, including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time to 90% PS (TPS90), time to 90% relengthening (TR90) and integration of shortening/relengthening (normalized to PS). Intracellular Ca2+ transients were evaluated using the following indices: resting and rise of fura-2 fluorescence intensity (ΔFFI) and intracellular Ca2+ decay time constant. 3. The results indicate that elevated extracellular Ca2+ stimulated cardiomyocyte positive inotrope, manifested as increased PS, ±dL/dt, area of shortening, resting FFI and ΔFFI associated with a shortened TR90 and intracellular Ca2+ decay time constant. High extracellular Ca2+ did not affect TPS90 and area of relengthening. Iodoacetamide ablated high Ca2+-induced increases in PS, ±dL/dt, area of shortening, resting FFI, ΔFFI and shortened TR90 and intracellular Ca2+ decay time constant. Iodoacetamide itself significantly enhanced the area of relengthening and TR90 without affecting other indices. 4. Collectively, these data demonstrate that inhibition of creatine kinase blunts high extracellular Ca2+-induced increases in cardiomyocyte contractile response (i.e. cardiac contractile reserve).
- Subjects
ENZYME inhibitors; CREATINE kinase; HEART cells; CARDIAC contraction
- Publication
Clinical & Experimental Pharmacology & Physiology, 2009, Vol 36, Issue 2, p141
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/j.1440-1681.2008.05034.x