Figure 3: Modulation of rCav1.3L and rbCav1.2S Ba2+ currents by Cp3 and Cp8.
From: Pyrimidine-2,4,6-triones are a new class of voltage-gated L-type Ca2+ channel activators
Representative traces for modulation of rCav1.3L (a) and rbCav1.2S (b) IBa in which tail currents were increased (Δtail) by 50 μM Cp8 (100 ms depolarizations, HP −80 mV to Vmax, 0.2 Hz). Last sweep before drug application (control) is shown in black, drug effect is shown 15 sweeps after application and 10 sweeps after starting washout. Dotted line: inhibition by 1 μM ISR after seven sweeps. Arrows indicate the peak of the tail current before drug application. Representative traces of modulation by 50 μM Cp8 of rCav1.3L (c) and rbCav1.2S (d) IBa in cells in which no pronounced increase in tail current (no Δtail) was observed. These recordings were analysed separately as described in the text (see also Table 2). Same protocol as in a and b, e and f, left: time course of the increase of the tail area for Δtail and no Δtail data sets of rCav1.3L (e) or rbCav1.2S (f). Recordings are shown for Cp8 (grey) and Cp3 (open). Controls were obtained in cells perfused only with bath solution containing 0.5% (v/v) DMSO using the same protocol. Right: effect of 50 μM Cp8 on IBa through rCav1.3L (e) and rbCav1.2S (f) at an early (4 ms for rCav1.3L, 7 ms for rbCav1.2S) and late (99 ms) time point. All n-values are given in parentheses. Means±s.e. are shown. Statistical significance was determined using unpaired t-test (control versus Cp8: ***P<0.001; **P<0.01; *P<0.05; Δtail versus no Δtail: ### P<0.001; #P<0.05) or paired t-test (early versus late time point: +++ P<0.001; ++ P<0.01).
