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.

+More

chelating cav22 voltageactivated cav3 calcium channels voltagedependent egta ca 2 domains small transient currents kca11cav kca11cav3 complexes hva cav channels concerted activity kca11cav22 model kca11 activation cav channel conductance regulation of kca11 activity calcium chelators

Jordan Dt, Engbers Gerald W, Zamponi Ray W, Turner,.Modeling interactions between voltage-gated Ca (2+) channels and KCa1.1 channels.. 7 (6),524-9.

Jordan Dt, Engbers Gerald W, Zamponi Ray W, Turner,"Modeling interactions between voltage-gated Ca (2+) channels and KCa1.1 channels." 7

Jordan Dt, Engbers Gerald W, Zamponi Ray W, Turner,"Modeling interactions between voltage-gated Ca (2+) channels and KCa1.1 channels."