Junctophilin Proteins Tether a Cav1-RyR2-KCa3.1 Tripartite Complex to Regulate Neuronal Excitability.

The excitability of CA1 hippocampal pyramidal cells is mediated by a slow AHP (sAHP) that responds to calcium increases by Cav1 calcium channels and ryanodine receptors (RyR). We used super-resolution and FRET microscopy to investigate the proximity and functional coupling among Cav1.3/Cav1.2, RyR2, and KCa3.1 potassium channels that contribute to ...
the sAHP. dSTORM and FRET imaging shows that Cav1.3, RyR2, and KCa3.1 are organized as a triprotein complex that colocalizes with junctophilin (JPH) 3 and 4 proteins that tether the plasma membrane to the endoplasmic reticulum. JPH3 and JPH4 shRNAs dissociated a Cav1.3-RyR2-KCa3.1 complex and reduced the IsAHP. Infusing JPH3 and JPH4 antibodies into CA1 cells reduced IsAHP and spike accommodation. These data indicate that JPH3 and JPH4 proteins maintain a Cav1-RyR2-KCa3.1 complex that allows two calcium sources to act in tandem to define the activation properties of KCa3.1 channels and the IsAHP.
Mesh Terms:
Action Potentials, Animals, CA1 Region, Hippocampal, Calcium Channels, L-Type, Cell Line, Cell Membrane, Cells, Cultured, Endoplasmic Reticulum, Female, Humans, Intermediate-Conductance Calcium-Activated Potassium Channels, Male, Membrane Proteins, Mice, Neurons, Rats, Rats, Sprague-Dawley, Ryanodine Receptor Calcium Release Channel
Cell Rep
Date: Dec. 27, 2018
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