Mg blocks the outward HCN2 current in the presence of physiological gradients of Na and K. (A and B) Averaged sweeps (A) and subtracted predeactivation HCN2 channel +80-mV tails (B) (three and two “leak” and “active” records collected as described in Fig. 3 except for the use of quasi-physiological gradients of Na and K, black lines). In B, the gray line is the K tail shown in Fig. 4 B scaled to the amplitude of Ip of the mixed ion tail. The red and green lines represent fits of a single exponential function and the resultant residuals for the two transients. (C) Plot of the extent (top) and time constant (bottom) of block at +80 mV in the presence of elevated K or physiological levels of Na and K in the extracellular solution. Data are mean ± SEM and range from five and two recordings, respectively.