Fractional-membrane association of PKA-C is important for its physiological function. (A) Simulation experiment showing that the observed moderate membrane affinity of full-length PKA-C is sufficient to enrich its activity at the membrane to over 19 times higher than its activity in the cytosol. (B and C) Representative traces (red) normalized to the paired control (blue) (insets) and scatter plots of paired AMPA (B) and NMDA (C) receptor currents from neighboring untransfected CA1 neurons paired with those transfected with shRNA against PKA-C and the indicated shRNA-resistant rescue constructs. Statistical P values were obtained using a sign test (MATLAB). From left to right, n = 12, 14, 19, and 15. *P ≤ 0.05 and is statistically significant after Bonferroni correction for multiple tests, **P ≤ 0.01, and ***P ≤ 0.001.