The effects of GAL-021 on breathing in isoflurane-anesthetized wild-type and pore-forming BKCa1.1 α subunit (Slo1−/−) knockout mice. Ventilatory parameters were measured using direct tracheal spirometry. GAL-021 (0 to 3 mg/kg) was administered intravenously as boluses using a cumulative dose paradigm. GAL-021 dose dependently increased (A) tidal volume (VT), (B) respiratory rate (RR), and (C) their product minute volume () above baseline values. (D) The change in expressed as percentage of baseline above baseline. (E) The peak percent change in was normalized to the mean maximal increase in at 3.0 mg/kg GAL-021 in the wild-type group and then a three-parameter nonlinear regression model applied to identify the best-fit curves. An equivalent volume of saline administered intravenously had no effect on minute volume. *Different from the knockout mouse GAL-021 group; #different from the wild-type saline group (two-way ANOVA, with Tukey multiple comparison tests; P < 0.05). Values are means ± SD, n = 6 for wild-type GAL-021 and wild-type saline groups, and n = 5 for the Slo1−/− group.