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. 2022 Dec 8;16:1054919. doi: 10.3389/fncel.2022.1054919

FIGURE 5.

FIGURE 5

Scheme of the main mechanisms involved in astrocyte volume changes and volume regulation in the acute post-ischemic phase, effect of AQP4 and TRPV4 channel deletion. Proposed mechanisms explaining the changes in the lesion size observed in the Ctrl (A), AQP4–/– (B), TRPV4–/– (C), and AQP4–/–/TRPV4–/– (D) mice. We propose that the absence of AQP4 in single (B) or double knock-outs (D) leads to slowed swelling that is insufficient to trigger regulatory volume decrease (RVD). Such a decrease in RVD presumably occurs due to low activity of TRPV4 channels, which is unable to activate SACs in panel (B), or lack of TRPV4 channels in panel (D). Water entry into the cell occurs via ion/glutamate transporters, while its efflux occurs besides ion channels by simple diffusion. Deletion of TRPV4 results in the absence of RVD activated by cell membrane stretch. Both slower swelling and limited RVD in double knock-outs, lead to less edema in the acute post-ischemic phase compared to control. Panels (B,D) both display limited swelling as well as RVD however in AQP4–/– (B) functional TRPV4 channels in neurons prolong neuronal activity with further neurotoxic impact on nervous tissue. A, astrocyte; N, neuron; Ctrl, control; AQP4–/–, AQP4-deficient mice; TRPV4–/–, TRPV4-deficient mice; AQP4–/–/TRPV4–/–, AQP4- and TRPV4-deficient mice; RVD, regulatory volume decrease; NKCC, Na+/K+/Cl– co-transporter; SAC, stretch activated ion channel; EAAT, excitatory amino acid transporter; AQP4, aquaporin-4 channel; TRPV4, Transient receptor potential cation channel subfamily V member 4.