Key result
Angiotensin II rapidly inhibits L-type calcium currents via CaVβ1b while sparing CaVβ2a channels.
Why the study?
Angiotensin II regulation of L-type calcium currents in cardiac muscle is controversial and the role of auxiliary Ca(v)β subunits in this modulation has not been explored.
Does not support clinical translation; extends mechanistic framework for Ang II effects on cardiac L-type currents via CaVβ isoforms.
Angiotensin 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.
No takes yet. Share an insight, caveat, or question.
Hermosilla et al. (2011) studied this question. Angiotensin II vs. Baseline (before AngII exposure) was evaluated on Percentage inhibition of L-type barium (calcium) current. Angiotensin II rapidly inhibits L-type calcium currents in a CaVβ subunit-dependent manner, with CaVβ1b channels being strongly regulated and CaVβ2a channels remaining largely insensitive.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: