Format

Send to

Choose Destination
See comment in PubMed Commons below
Arch Biochem Biophys. 2013 Oct 15;538(2):130-7. doi: 10.1016/j.abb.2013.08.007. Epub 2013 Aug 27.

The membrane potential modulates thrombin-stimulated Ca²⁺ mobilization and platelet aggregation.

Author information

1
Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.

Abstract

G protein-coupled receptors can be directly modulated by changes in transmembrane voltage in a variety of cell types. Here we show that, while changes in the membrane voltage itself do not induce detectable modifications in the cytosolic Ca(2+) concentration, platelet stimulation with thrombin or the PAR-1 and PAR-4 agonist peptides SFLLRN and AYPGKF, respectively, results in Ca(2+) release from intracellular stores that is sensitive to the membrane depolarisation. Direct activation of G proteins or phospholipase C by AlF4(-) and m-3M3FBS, respectively, leads to Ca(2+) release that is insensitive to changes in the membrane potential. Thapsigargin-, as well as OAG-induced Ca(2+) entry are affected by the membrane voltage, probably as a result of the modification in the driving force for Ca(2+) influx; however, hyperpolarisation does not enhance thrombin- or OAG-evoked Ca(2+) entry probably revealing the presence of a voltage-sensitive regulatory mechanism. Transmembrane voltage also modulates the activity of the plasma membrane Ca(2+)-ATPase (PMCA) most likely due to a decrease in the phosphotyrosine content of the pump. Thrombin-stimulated platelet aggregation is modulated by membrane depolarisation by a mechanism that is, at least partially, independent of Ca(2+). These observations indicate that PAR-1 and PAR-4 receptors are modulated by the membrane voltage in human platelets.

KEYWORDS:

Aggregation; Ca(2+) entry; Ca(2+) release; Human platelets; Membrane potential; Thrombin

PMID:
23988350
DOI:
10.1016/j.abb.2013.08.007
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center