Calcium induced calcium release in proximity to hair cell BK channels revealed by PKA activation

Abstract Large conductance calcium-activated potassium (BK) channels play a critical role in electrical resonance, a mechanism of frequency selectivity in chicken hair cells. We determine that BK currents are dependent on inward flow of Ca 2+ , and intracellular buffering of Ca 2+ . Entry of Ca 2+ is further amplified locally by Ca 2+ induced Ca 2+ release (CICR) in close proximity to plasma membrane BK channels. Ca 2+ imaging reveals peripheral clusters of high concentrations of Ca 2+ that are suprathreshold to that needed to activate BK channels. PKA activation increases BK currents likely by recruiting more BK channels due to spatial spread of high Ca 2+ concentrations in turn from increasing CICR. STORM imaging confirms the presence of nanodomains with ryanodine and IP3 receptors in close proximity to the Slo subunit of BK channels. Together, these data require a rethinking of how electrical resonance is brought about and suggest effects of CICR in synaptic release. Both genders were included in this study.