Figure 2.
TRPV4 activation massively elevates Müller cell calcium levels. A, GSK101 dose-dependently increases calcium levels above spontaneous calcium spikes. B, The amplitude of Müller cell responses to GSK101 was quantified using fura-5F. n = 14, 12, and 4, respectively. C, 25 nm GSK101 increased calcium levels far more than other known modulators of Müller cell calcium homeostasis. n = 33, 26, 25, 19, and 19, respectively. D, According to the sigmoidal fit, the EC50 of GSK101 was ∼16 nm. n = 12. E, GSK101 induced a current with an IV plot characteristic of heteromeric TRPV4. Light gray trace represents voltage ramp-induced transmembrane current under resting conditions. Gray trace represents GSK101-induced current. Black trace represents difference current after subtraction. n = 10. F, TRPV4 opening by GSK101 resulted in a large inward conductance that coincided with an elevation in calcium. NS, Not significant (p > 0.05). ****p < 0.0001.