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. 2023 May 4;299(6):104782. doi: 10.1016/j.jbc.2023.104782

Figure 1.

Figure 1

Poking-evoked PIEZO2-mediated whole-cell currents are regulated by PKA.A, schematic representation of the possible cAMP-dependent cellular signaling cascade (PKA or EPAC1/2) potentiating PIEZO2, in addition to their respective pharmacological modulators used throughout the study. B, cartoon depicting the recording paradigm (left) and representative PIEZO2 whole-cell currents (holding −60 mV) evoked by increasing mechanical indentation of N2a-P1KO cells (right) in the absence (black) or in the presence of the PKA activator 8-bromo-cAMP (green), the PKA and PKC inhibitors GF and KT (gray) and of the EPAC1/2 activator 8-pCPT (purple). C, displacement–response curves (left) and scatter plot (right) of maximal peak current amplitudes of poking-evoked currents recorded from N2a cells expressing PIEZO2 and treated with the indicated drugs. Data are presented as the mean ± SD. Number of cells per group is indicated in the legend. Comparison with Kruskal–Wallis test p < 0.0001 and Dunn’s post-test p < 0.05 ∗, p < 0.001 ∗∗, p < 0.0001 ∗∗∗, 8-Br-cAMP versus untreated. See also Fig. S1. D, mechanical activation thresholds of PIEZO2 whole-cell currents from treated and untreated cells. Data are presented as the mean ± SD with individual values. Untreated N = 10, GF + KT N = 11, 8-Br-cAMP N = 14, and 8-pCPT N = 17. Comparison with one-way ANOVA F(3, 52) = 5.69, p = 0.0019 and Tukey’s post-test, KT versus 8Br p = 0.0049 and 8Br versus 8pCPT p = 0.0029. E, inactivation time constants (τinact) of PIEZO2 whole-cell currents from treated and untreated cells. Data are presented as the mean ± SD with individual values. Untreated N = 10, GF + KT N = 13, 8-Br-cAMP N = 16, and 8-pCPT N = 19. Comparison with Kruskal–Wallis test p = 0.0251 and Dunn’s post-test, p = 0.023 KT versus 8Br. See also Fig. S1. 8-Br-cAMP, 8-bromo-cyclic-AMP.