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Calcium-dependent enhancement of calcium current in smooth muscle by calmodulin-dependent protein kinase II

Abstract

CALCIUM entry through voltage-activated Ca2+ channels is important in regulating many cellular functions. Activation of these channels in many cell types results in feedback regulation of channel activity1. Mechanisms linking Ca2+ channel activity with its downregulation have been described2,3, but little is known of the events responsible for the enhancement of Ca2+ current that in many cells follows Ca2+ channel activation and an increase in cytoplasmic Ca2+ concentration4,5. Here we investigate how this positive feedback is achieved in single smooth muscle cells. We find that in these cells voltage-activated calcium current is persistently but reversibly enhanced after periods of activation. This persistent enhancement of the Ca2+ current is mediated by activation of calmodulin-dependent protein kinase II because it is blocked when either the rise in cytoplasmic Ca2+ is inhibited or activation of calmodulin-dependent protein kinase II is prevented by specific peptide inhibitors of calcium-calmodulin or calmodulin-dependent protein kinase II itself. This mechanism may be important in different forms of Ca2+ current potentiation, such as those that depend on prior Ca2+ channel activation or are a result of agonist-induced release of Ca2+ from internal stores.

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McCarron, J., McGeown, J., Reardon, S. et al. Calcium-dependent enhancement of calcium current in smooth muscle by calmodulin-dependent protein kinase II. Nature 357, 74–77 (1992). https://doi.org/10.1038/357074a0

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