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Intracellular Effects of Nitric Oxide on Force Production and Ca2+Sensitivity of Cardiac Myofilaments
- Source :
- Antioxidants & Redox Signaling. 1:509-521
- Publication Year :
- 1999
- Publisher :
- Mary Ann Liebert Inc, 1999.
-
Abstract
- The gaseous free radical nitric oxide (NO*) has been implicated in a wide range of physiological functions and also has a role in the pathogenesis of cellular injury. It has been suggested that NO* and its congeners may exert effects on actin-myosin crossbridge cycling by modulating critical thiols on the myosin head. To understand the mode and site of actin of NO* in myofibrils, the effects of the NO* donor 3-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl-1-propanamine (NOC-7) have been studied in Triton X-100-treated rabbit cardiac fibers, in which isometric force was measured at controlled degrees of activation. Experiments were undertaken after previous exposure of the preparations to NOC-7 (for 30 min). We found that NO* induced several alterations of myofibrillar function, i.e., decrease in Ca2+ sensitivity and Hill coefficient and potentiation of rigor contracture. We attributed the effect on rigor contracture to strong inhibition of myofibrillar creatine kinase (CK) activity, because it could be prevented by exogeneously added CK; such CK inactivation afforded by NO* may result in the myofibrillar ATP-to-ADP ratio. In further experiments, concentration of NO* released from NOC-7 was determined by the electron spin resonance spin-trapping technique; N-(dithiocarboxy)sarcosine-Fe2+ complex was used as the spin-trap. NO* at cumulative concentration of 0.69 microM was effective in producing both enhancement of rigor contracture and decrease of myofibrillar-bound CK activity; however, Ca2+-sensitivity (pCa50) was significantly decreased at5.6 microM of NO*, suggesting a result from different mechanisms. Thus, the observed decrease in Ca2+ sensitivity seems to be associated with direct modification of the regulatory proteins by a relatively higher concentration of NO*, and possibly not via inhibition of myofibrillar CK activity. The data reported here indicate that CK may be a pathophysiologically main target for increased NO* formation at low molecular range in the disease state in cardiac muscle.
- Subjects :
- Male
Myofilament
Time Factors
Physiology
Clinical Biochemistry
macromolecular substances
In Vitro Techniques
Nitric Oxide
Biochemistry
Nitric oxide
Myosin head
chemistry.chemical_compound
Adenosine Triphosphate
CrossBridge
Animals
Nitric Oxide Donors
Creatine Kinase
Molecular Biology
Actin
General Environmental Science
biology
Chemistry
Myocardium
Electron Spin Resonance Spectroscopy
Heart
Cell Biology
Myocardial Contraction
Actin Cytoskeleton
Hydrazines
biology.protein
Biophysics
General Earth and Planetary Sciences
Calcium
Creatine kinase
Rabbits
Myofibril
Spin Trapping
Intracellular
Subjects
Details
- ISSN :
- 15577716 and 15230864
- Volume :
- 1
- Database :
- OpenAIRE
- Journal :
- Antioxidants & Redox Signaling
- Accession number :
- edsair.doi.dedup.....c4db4f41734cc8857eeaa057af0011f8