Figure 4.
Figure 4. The transient outward current is carried by the HCN2 channels. (A1) HCN2 currents obtained before (black), during (blue), and after (gray) application of 300 μM ZD7288 (ionic conditions and voltage paradigms as in Fig. 3). Each trace is the average of eight sweeps evoked in response to the 3-ms “active” protocol before subtraction of the interlaced “leak” sweeps (records not shown for simplicity). Currents were filtered and sampled at 20 and 100 kHz, respectively. (A2) Expanded views of the +80 mV sojourn following subtraction of the appropriate “leak” records before (raw) and after (scaled) scaling each trace to the amplitude of the preZD7288 −135 mV current (I –135). (A3) ZD7288-sensitive component of the current (obtained as the difference between the leak-subtracted pre and plus ZD7288 records in “A2, raw”) is shown before (subtracted) and after (subtracted and scaled) scaling the blocked component (blue traces) to the preZD7288 I –135 amplitude. (B) Outward transient in the absence of ZD7288 (black line) with superimposed fit of a single-exponential function (red line). Residuals from the fit (green line) are offset from zero for clarity. Arrows show the amplitudes of the plateau (Ip) and transient (It) components of the outward current. (C) Fractional ZD7288 inhibition of I –135, It, and Ip, where IC is the control amplitude and IZ the 300 μM ZD7288-resistant amplitude, respectively. Data are mean ± SEM from three recordings acquired and analyzed as described in A and B. (D and E) Linear regressions (superimposed lines) show the amplitudes of It (R2 = 0.955) and Ip (R2 = 0.986) are highly correlated with that of I –135 (D) and with each other (E; R2 = 0.945). Data are from seven independent patches. (F) Time constant of current decay at +80 mV as a function of the I –135 amplitude. The black line is a linear regression (R2 = 0.070) across the control data from seven independent recordings. Red lines connect data acquired in three independent recordings before, during, and after cut down of the current by inclusion of ZD7288 (data points obtained before and after washout of ZD7288 in the same patch are ringed by a red ellipse).

The transient outward current is carried by the HCN2 channels. (A1) HCN2 currents obtained before (black), during (blue), and after (gray) application of 300 μM ZD7288 (ionic conditions and voltage paradigms as in Fig. 3). Each trace is the average of eight sweeps evoked in response to the 3-ms “active” protocol before subtraction of the interlaced “leak” sweeps (records not shown for simplicity). Currents were filtered and sampled at 20 and 100 kHz, respectively. (A2) Expanded views of the +80 mV sojourn following subtraction of the appropriate “leak” records before (raw) and after (scaled) scaling each trace to the amplitude of the preZD7288 −135 mV current (I –135). (A3) ZD7288-sensitive component of the current (obtained as the difference between the leak-subtracted pre and plus ZD7288 records in “A2, raw”) is shown before (subtracted) and after (subtracted and scaled) scaling the blocked component (blue traces) to the preZD7288 I –135 amplitude. (B) Outward transient in the absence of ZD7288 (black line) with superimposed fit of a single-exponential function (red line). Residuals from the fit (green line) are offset from zero for clarity. Arrows show the amplitudes of the plateau (Ip) and transient (It) components of the outward current. (C) Fractional ZD7288 inhibition of I –135, It, and Ip, where IC is the control amplitude and IZ the 300 μM ZD7288-resistant amplitude, respectively. Data are mean ± SEM from three recordings acquired and analyzed as described in A and B. (D and E) Linear regressions (superimposed lines) show the amplitudes of It (R2 = 0.955) and Ip (R2 = 0.986) are highly correlated with that of I –135 (D) and with each other (E; R2 = 0.945). Data are from seven independent patches. (F) Time constant of current decay at +80 mV as a function of the I –135 amplitude. The black line is a linear regression (R2 = 0.070) across the control data from seven independent recordings. Red lines connect data acquired in three independent recordings before, during, and after cut down of the current by inclusion of ZD7288 (data points obtained before and after washout of ZD7288 in the same patch are ringed by a red ellipse).

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