L-type calcium channel β subunit modulates angiotensin II responses in cardiomyocytes

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dc.contributor.authorHermosilla, Tamara
dc.contributor.authorMoreno, Cristian
dc.contributor.authorItfinca, Mircea
dc.contributor.authorAltier, Christophe
dc.contributor.authorArmisén, Ricardo
dc.contributor.authorStutzin, Andrés
dc.contributor.authorZamponi, Gerald W.
dc.contributor.authorVarela, Diego L.
dc.date.accessioned2018-05-23T20:30:14Z
dc.date.available2018-05-23T20:30:14Z
dc.date.issued2011-05
dc.description.abstractAngiotensin II regulation of L-type calcium currents in cardiac muscle is controversial and the underlying signaling events are not completely understood. Moreover, the possible role of auxiliary subunit composition of the channels in Angiotensin II modulation of L-type calcium channels has not yet been explored. In this work we study the role of Ca(v)β subunits and the intracellular signaling responsible for L-type calcium current modulation by Angiotensin II. In cardiomyocytes, Angiotensin II exposure induces rapid inhibition of L-type current with a magnitude that is correlated with the rate of current inactivation. Semi-quantitative PCR of cardiomyocytes at different days of culture reveals changes in the Ca(v)β subunits expression pattern that are correlated with the rate of current inactivation and with Angiotensin II effect. Over-expression of individual b subunits in heterologous systems reveals that the magnitude of Angiotensin II inhibition is dependent on the Ca(v)β subunit isoform, with Ca(v)β(1b) containing channels being more strongly regulated. Ca(v)β(2a) containing channels were insensitive to modulation and this effect was partially due to the N-terminal palmitoylation sites of this subunit. Moreover, PLC or diacylglycerol lipase inhibition prevents the Angiotensin II effect on L-type calcium channels, while PKC inhibition with chelerythrine does not, suggesting a role of arachidonic acid in this process. Finally, we show that in intact cardiomyocytes the magnitude of calcium transients on spontaneous beating cells is modulated by Angiotensin II in a Ca(v)β subunit-dependent manner. These data demonstrate that Ca(v)β subunits alter the magnitude of inhibition of L-type current by Angiotensin II.en_US
dc.identifier.citationHermosilla, T., Moreno, C., Itfinca, M., Altier, C., Armisén, R., Stutzin, A., … Varela, D. (2011). L-type calcium channel β subunit modulates angiotensin II responses in cardiomyocytes. Channels, 5(3). https://doi.org/10.4161/chan.5.3.15833en_US
dc.identifier.doidoi.org/10.4161/chan.5.3.15833en_US
dc.identifier.urihttp://hdl.handle.net/1880/106655
dc.language.isoenen_US
dc.publisherTaylor and Francisen_US
dc.publisher.departmentPhysiology & Pharmacologyen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.titleL-type calcium channel β subunit modulates angiotensin II responses in cardiomyocytesen_US
dc.typeunknown
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