Depotentiation of intact rat cardiac muscle unmasks an Epac-dependent increase in myofilament Ca(2+) sensitivity

Show simple item record Kaur, Sarbjot en Kong, CHT en Cannell, MB en Ward, Marie-Louise en 2016-05-13T00:50:42Z en 2016-01 en
dc.identifier.citation Clinical and Experimental Pharmacology and Physiology, 2016, 43 (1), pp. 88 - 94 en
dc.identifier.issn 1440-1681 en
dc.identifier.uri en
dc.description.abstract Recently, a family of guanine nucleotide exchange factors have been identified in many cell types as important effectors of cyclic adenosine 3',5'-monophospahte (cAMP) signalling that is independent of protein kinase A (PKA). In the heart, investigation of exchange protein directly activated by cAMP (Epac) has yielded conflicting results. Since cAMP is an important regulator of cardiac contractility, this study aimed to examine whether Epac activation modulates excitation-contraction coupling in ventricular preparations from rat hearts. The study used 8-(4-chlorophenylthio)-2'-O-methyladenosine-3', 5'-cyclic monophosphate (cpTOME), an analogue of cAMP that activates Epac, but not PKA. In isolated myocytes, cpTOME increased Ca(2+) spark frequency from about 7 to 32/100 μm(3)/s (n = 10), P = 0.05 with a reduction in the peak amplitude of the sparks. Simultaneous measurements of intracellular Ca(2+) and isometric force in multicellular trabeculae (n = 7, 1.5 mmol/L [Ca(2+)]o) revealed no effect of Epac activation on either the amplitude of Ca(2+) transients (Control 0.7 ± 0.1 vs cpTOME 0.7 ± 0.1; 340/380 fura-2 ratio, P = 0.35) or on peak stress (Control 24 ± 5 mN/mm(2) vs cpTOME 23 ± 5 mN/mm(2), P = 0.20). However, an effect of Epac in trabeculae was unmasked by lowering extracellular [Ca(2+)]o. In these depotentiated trabeculae, activation of the Epac pathway increased myofilament Ca(2+) sensitivity, an effect that was blocked by addition of KN-93, a Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II) inhibitor. This study suggests that Epac activation may be a useful therapeutic target to increase the strength of contraction during low inotropic states. en
dc.format.medium Print en
dc.language eng en
dc.publisher Wiley: 12 months en
dc.relation.ispartofseries Clinical and Experimental Pharmacology and Physiology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.title Depotentiation of intact rat cardiac muscle unmasks an Epac-dependent increase in myofilament Ca(2+) sensitivity en
dc.type Journal Article en
dc.identifier.doi 10.1111/1440-1681.12504 en
pubs.issue 1 en
pubs.begin-page 88 en
pubs.volume 43 en
dc.rights.holder Copyright: Wiley: 12 months en
dc.identifier.pmid 26466753 en
pubs.end-page 94 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 502746 en Medical and Health Sciences en Medical Sciences en Physiology Division en
dc.identifier.eissn 1440-1681 en
pubs.record-created-at-source-date 2016-05-13 en
pubs.dimensions-id 26466753 en

Files in this item

There are no files associated with this item.

Find Full text

This item appears in the following Collection(s)

Show simple item record


Search ResearchSpace