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PMID:2530435

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Citation

Solaro, RJ, el-Saleh, SC and Kentish, JC (1989) Ca2+, pH and the regulation of cardiac myofilament force and ATPase activity. Mol. Cell. Biochem. 89:163-7

Abstract

When the pH surrounding myofilaments of striated muscle is reduced there is an inhibition of both the actin-myosin reaction as well as the Ca2+-sensitivity of the myofilaments. Although the mechanism for the effect of acidic pH on Ca2+-sensitivity has been controversial, we have evidence for the hypothesis that acidic pH reduces the affinity of troponin C (TNC) for Ca2+. This effect of acidic pH depends not only on a direct effect of protons on Ca2+-binding to TNC, but also upon neighboring thin filament proteins, especially TNI, the inhibitory component of the TN complex. Using fluorescent probes that report Ca2+-binding to the regulatory sites of skeletal and cardiac TNC, we have shown, for example, that acidic pH directly decreases the Ca2+-affinity of TNC, but only by a relatively small amount. However, with TNC in whole TN or in the TNI-TNC complex, there is about a 2-fold enhancement of the effects of acidic pH on Ca2+-binding to TNC. Acidic pH decreases the affinity of skeletal TNI for skeletal TNC, and also influences the micro-environment of a probe positioned at Cys-133 of TNI, a region of interaction with TNC. Other evidence that the effects of acidic pH on Ca2+-TNC activation of myofilaments are influenced by TNI comes from studies with developing hearts. In contrast, to the case with the adult preparations, Ca2+-activation of detergent extracted fibers prepared from dog or rat hearts in the peri-natal period are weakly affected by a drop in pH from 7.0 to 6.5. This difference in the effect of acidic pH appears to be due to a difference in the isoform population of TNI, and not to differences in isotype population or amount of TNC.

Links

PubMed

Keywords

Actin Cytoskeleton/enzymology; Actin Cytoskeleton/metabolism; Adenosine Triphosphatases/metabolism; Animals; Calcium/metabolism; Cytoskeleton/metabolism; Fluorescent Dyes; Hydrogen-Ion Concentration; Muscles/metabolism; Myocardial Contraction/physiology; Myocardium/enzymology; Myocardium/metabolism; Rats; Troponin/metabolism; Troponin C; Troponin I

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TNNT2

involved_in

GO:0051592: response to calcium ion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TNNT2

contributes_to

GO:0016887: ATPase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TNNT2

part_of

GO:0005861: troponin complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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