Modeling interactions between voltage-gated Ca2+ channels and KCa1.1 channels

• Published in: Channels (Austin, Tex.) Vol. 7; no. 6; pp. 524 - 529
• Main Authors: Engbers, Jordan DT, Zamponi, Gerald W, Turner, Ray W
• Format: Journal Article
• Language: English
• Published: Taylor & Francis 02.11.2013; Landes Bioscience
• Subjects: Addendum; Cav2.2; Cav3; ion channel complex; KCa1.1
• ISSN: 1933-6950; 1933-6969
• DOI: 10.4161/chan.25867

High voltage-activated (HVA) Cav channels form complexes with KCa1.1 channels, allowing reliable activation of KCa1.1 current through a nanodomain interaction. We recently found that low voltage-activated Cav3 calcium channels also create KCa1.1-Cav3 complexes. While coimmunoprecipitation studies again supported a nanodomain interaction, the sensitivity to calcium chelating agents was instead consistent with a microdomain interaction. A computational model of the KCa1.1-Cav3 complex suggested that multiple Cav3 channels were necessary to activate KCa1.1 channels, potentially causing the KCa1.1-Cav3 complex to be more susceptible to calcium chelators. Here, we expanded the model and compared it to a KCa1.1-Cav2.2 model to examine the role of Cav channel conductance and kinetics on KCa1.1 activation. As found for direct recordings, the voltage-dependent and kinetic properties of Cav3 channels were reflected in the activation of KCa1.1 current, including transient activation from lower voltages than other KCa1.1-Cav complexes. Substantial activation of KCa1.1 channels required the concerted activity of several Cav3.2 channels. Combined with the effect of EGTA, these results suggest that the Ca 2+ domains of several KCa1.1-Cav3 complexes need to cooperate to generate sufficient [Ca 2+ ] i , despite the physical association between KCa1.1 and Cav3 channels. By comparison, Cav2.2 channels were twice as effective at activating KCa1.1 channels and a single KCa1.1-Cav2.2 complex would be self-sufficient. However, even though Cav3 channels generate small, transient currents, the regulation of KCa1.1 activity by Cav3 channels is possible if multiple complexes cooperate through microdomain interactions.