Figure 3.

Aging impairs SK_Ca/IK_Ca channel function for V_m hyperpolarization in females but not males. Representative simultaneous recordings of (A) a sharp electrode for V_m and (B) Fura-2 for [Ca²⁺]_i before and during NS309 (0.1–10 µmol/L; direct SK_Ca/IK_Ca channel activator) in an isolated endothelial tube of a young male. (C) Summary data for ∆V_m during NS309 as a function of age (Young, Middle, Old) according to male sex. (D) Summary data for ΔF₃₄₀/F₃₈₀ as a function of age (Young, Middle, Old) according to male sex. (E, F) As shown in (C) and (D), respectively, for female sex. (G) Summary data for ∆V_m as a function of age (Young, Middle, Old) and sex (Male, Female) as (C) and (E) together. (H) As shown in (G) for ΔF₃₄₀/F₃₈₀ as (D) and (F) together. (I) Summary data for ∆V_m during NS309 as a function of age only (sexes combined). (J) As shown in I for ΔF₃₄₀/F₃₈₀ as a function of age only (sexes combined). N = number of cerebral endothelial tubes (Young, Middle, and Old: 5, 5, and 5 Males and 5, 6, and 5 Females; combined for age only: 10, 11, and 10). *p < .05, Old versus Young and/or Middle for same sex; #p < .05, Female versus Male for Old. YM: Young male; MM; Middle male; OM: Old male; YF: Young female; MF: Middle female; OF: Old female. Note that ∆[Ca²⁺]_i follows ∆V_m responses to NS309. Hyperpolarization responses were decreased to effective concentrations of NS309 (0.3 to 1 µmol/L) in old females as a function of age (vs young) and sex (vs old male). See Results for respective pEC₅₀ values indicating OF < YF or OM. Subsequent ∆[Ca²⁺]_i responses during old age increased for males and decreased for females. With data from respective sexes combined, such differences with age are no longer apparent.