Effects of replacing extracellular Na+ with mannitol, choline, or monovalent cations on Slo2.1 channel currents. (A–E) ISlo2.1-V relationships for oocytes bathed in KCM411 extracellular solution and activated by 1 mM NFA before and after replacement of extracellular Na+ with either mannitol or indicated monovalent cation. (A and B) Currents recorded from oocytes 3 d after injection with 0.32 ng cRNA (n = 6). (C and D) Currents recorded from oocytes 3 d after injection with 0.84 ng cRNA (n = 5–6). (D, inset) Currents for Vt of −60 to −160 mV at an expanded scale. (F) ISlo2.1–V relationships for oocytes activated by 3 mM NFA and bathed in an extracellular solution containing the indicated level (in mM) of NaCl. [Na+]e was varied from 0 to 90 mM by substitution with mannitol to maintain constant osmolarity (n = 6). Currents were recorded 3 d after injection of oocytes with 0.32 ng cRNA. Inset shows plot of maximum slope conductance as a function of log10[Na+]e. Data were fitted to a Hill equation (smooth curve; EC50 = 10.5 ± 4.2 mM, nH = 0.72 ± 0.13, and R2 = 0.997).