A specific cyclic ADP-ribose antagonist inhibits cardiac excitation-contraction coupling
| Autor: | Gloria A. Ashamu, Barry V. L. Potter, Derek A. Terrar, Antony Galione, Stevan Rakovic |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
Contraction (grammar) Guinea Pigs Biology In Vitro Techniques Cyclic ADP-ribose Ryanodine receptor 2 General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Myocyte Animals Humans 030304 developmental biology 0303 health sciences Adenosine Diphosphate Ribose Cyclic ADP-Ribose Agricultural and Biological Sciences(all) Ryanodine receptor Biochemistry Genetics and Molecular Biology(all) Endoplasmic reticulum Cardiac muscle Myocardial Contraction Endocrinology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Microsome Biophysics Calcium Calcium Channels General Agricultural and Biological Sciences |
| Zdroj: | Current biology : CB. 6(8) |
| ISSN: | 0960-9822 |
| Popis: | Background Cyclic ADP-ribose (cADPR) has been shown to act as a potent cytosolic mediator in a variety of tissues, regulating the release of Ca 2 + from intracellular stores by a mechanism that involves ryanodine receptors. There is controversy over the effects of cADPR in cardiac muscle, although one possibility is that endogenous cADPR increases the Ca 2 + sensitivity of Ca 2 + -induced Ca 2 + release (CICR) from the sarcoplasmic reticulum. We investigated this possibility using 8-amino-cADPR, which has been found to antagonize the Ca 2 + -releasing effects of cADPR on sea urchin egg microsomes and in mammalian cells (Purkinje neurons, Jurkat T cells, smooth muscle and PC12 cells). Results In intact cardiac myocytes isolated from guinea-pig ventricle, cytosolic injection of 8-amino-cADPR substantially reduced contractions and Ca 2 + transients accompanying action potentials (stimulated at 1Hertz). These reductions were not seen with injection of HEPES buffer, with heat-inactivated 8-amino-cADPR, or in cells pretreated with ryanodine (2 μ M) to suppress sarcoplasmic reticulum function before injection of the 8-amino-cADPR. L-type Ca 2 + currents and the extent of Ca 2 + loading of the sarcoplasmic reticulum were not reduced by 8-amino-cADPR. Conclusions These observations are consistent with the hypothesis that endogenous cADPR plays an important role during normal contraction of cardiac myocytes. One possibility is that cADPR sensitizes the CICR mechanism to Ca 2 + , an action antagonized by 8-amino-cADPR (leading to reduced Ca 2 + transients and contractions). A direct effect of 8-amino-cADPR on CICR cannot be excluded, but observations with caffeine are not consistent with a non-selective block of release channels. |
| Databáze: | OpenAIRE |
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