The L-type calcium channel current modulation mechanism: the plot thickens and fogs
Brooke M. Ahern, Jonathan Satin
Brooke M. Ahern, Jonathan Satin
Published January 7, 2019
Citation Information: J Clin Invest. 2019;129(2):496-498. https://doi.org/10.1172/JCI125958.
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Commentary

The L-type calcium channel current modulation mechanism: the plot thickens and fogs

Abstract

Stressful situations provoke the fight-or-flight response, incurring rapid elevation of cardiac output via activation of protein kinase A (PKA). In this issue of the JCI, Yang et al. focus on the L-type calcium channel complex (LTCC), and their findings require reexamination of dogmatic principles. LTCC phosphorylation sites identified and studied to date are dispensable for PKA modulation of LTCC; however, a CaVβ2-CaV1.2 calcium channel interaction is now shown to be required. Yang et al. suggest a new hypothesis that LTCC modulation involves rearrangement of auxiliary proteins within the LTCC. However, we still do not know the targets of PKA that mediate LTCC modulation.

Authors

Brooke M. Ahern, Jonathan Satin

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Figure 1

CaVβ2-CaV1.2 interaction is not required for forward trafficking, but is required for CaV1.2 modulation by PKA.

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CaVβ2-CaV1.2 interaction is not required for forward trafficking, but is...
(A) Old dogma: CaVβ-CaVα interaction on the Golgi apparatus promotes forward trafficking. CaV1.2 in the transverse tubules is modulated by one or more phosphoregulatory sites on CaV1.2 and/or CaVβ2. (B) New paradigm: CaVβ-CaVα interaction is not required for forward trafficking, and in the transverse tubules CaV1.2 modulation requires CaVβ, and perhaps additional accessory subunits.