Figure 5. SUR1-TRPM4 synergizes with AQP4 to mediate cellular water uptake and swelling.

(A) Traces of calcein fluorescence (F_t/F₀) in COS-7 cells showing that, compared to expression of empty vector (CTR), expression of AQP4 M1 or M23 in COS-7 cells results in hypotonic stress-induced swelling. (B, C) Traces of calcein fluorescence in COS-7 cells showing that, compared to control conditions (green, pink, and blue), expression of TRPM4 (orange) sensitizes COS-7 cells to Ca²⁺ ionophore A23187-induced water influx, which is increased in rate upon co-expression of AQP4 M1 (black) or M23 (red) (B) and blocked by treatment with the TRPM4 antagonist 9-phenanthrol (C). (D, E) Traces of calcein fluorescence in COS-7 cells showing that, compared to control conditions (blue, pink, grey), A23187-induced water influx in TRPM4-expressing COS-7 cells (orange) is increased in magnitude upon co-expression of SUR1 (green), further increased in both magnitude and rate upon co-expression of SUR1 and AQP4 M1 (black) or M23 (red) (D), and inhibited by the SUR1 antagonist glibenclamide to levels similar to TRPM4-expressing cells (E); n=3 independent experiments with 3 cells/experiment; *p<0.05 in ANOVA with Tukey tests versus leftmost column or between groups denoted with brackets.