Ca2+-calmodulin-dependent protein kinase II potentiates store-operated Ca2+ current.
A rise in intracellular Ca2+ (Ca2+i) mediates various cellular functions ranging from fertilization to gene expression. A ubiquitous Ca2+ influx pathway that contributes significantly to the generation of Ca2+i signals, especially in non-excitable cells, is store-operated Ca2+ entry (SOCE). Consequently, the modulation of SOCE current affects Ca2+i dynamics and thus the ensuing cellular response. Therefore, it is important to define the mechanisms that regulate SOCE. Here we show that a rise in Ca2+i potentiates SOCE. This potentiation is mediated by Ca2+-calmodulin-dependent protein kinase II (CaMKII), because inhibition of endogenous CaMKII activity abrogates Ca2+i-mediated SOCE potentiation and expression of constitutively active CaMKII potentiates SOCE current independently of Ca2+i. Moreover, we present evidence that CaMKII potentiates SOCE by altering SOCE channel gating. The regulation of SOCE by CaMKII defines a novel modulatory mechanism of SOCE with important physiological consequences.
Machaca
Khaled
K
Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. machacakhaleda@uams.edu
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D004594:Electrophysiology; D015640:Ion Channel Gating; D007700:Kinetics; D018613:Microscopy, Confocal; D009865:Oocytes / Q000378:metabolism; D010766:Phosphorylation; D011985:Receptors, Serotonin / Q000378:metabolism; D013997:Time Factors; D014982:Xenopus laevis
D015220:Calcium Channels; D011985:Receptors, Serotonin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium