text{BK}_{\text{Ca}}$-Cav Channel Complexes Mediate Rapid and Localized$\text{Ca}^{2+}$-Activated K⁺ Signaling

Large-conductance calcium- and voltage-activated potassium channels ($\text{BK}_{\text{Ca}}$) are dually activated by membrane depolarization and elevation of cytosolic calcium ions ($\text{Ca}^{2+}$). Under normal cellular conditions,$\text{BK}_{\text{Ca}}$channel activation requires$\text{Ca}^{2+}$concentrations that typically occur in close proximity to$\text{Ca}^{2+}$sources. We show that$\text{BK}_{\text{Ca}}$channels affinity-purified from rat brain are assembled into macromolecular complexes with the voltage-gated calcium channels Cav1.2 (L-type), Cav2.1 (P/Q-type), and Cav2.2 (N-type). Heterologously expressed$\text{BK}_{\text{Ca}}$-Cav complexes reconstitute a functional "$\text{Ca}^{2+}$nanodomain" where$\text{Ca}^{2+}$influx through the Cav channel activates$\text{BK}_{\text{Ca}}$in the physiological voltage range with submillisecond kinetics. Complex formation with distinct Cav channels enables$\text{BK}_{\text{Ca}}$-mediated membrane hyperpolarization that controls neuronal firing pattern and release of hormones and transmitters in the central nervous system.