Table 1.
Effects of PQ on hemodynamic and electrocardiographic variables in anesthetized rats.
Fig 1.
Representative recordings of arterial pressure, LV pressure (LVP), first derivative of LV pressure (LV dP/dt), and ECG from an anesthetized rat at baseline and at various times after PQ treatment (180 mg/kg, i.v.).
QTc value in each panel denotes rate-corrected QT interval derived using normalized Bazett’s formula QTc = QT/(RR/f)1/2, where f = 180 ms.
Fig 2.
Representative tracings of LVP (upper) and dP/dt (lower) signals recorded from Langendorff-perfused rat hearts paced at 300 beats/min at baseline and following treatment with 33 μM (A) or 60 μM PQ (B).
Fig 3.
Effects of PQ on Ca2+ transients (represented by fura-2 fluorescence ratio F340/F380) and cell shortening in rat ventricular myocytes paced at 1 Hz.
(A) Continuous recordings of Ca2+ transients (upper panel) and cell shortening (lower panel) showing the effects of the cumulative application of 10, 30, and 60 μM PQ. (B) Recordings on an expanded time scale taken at the time indicated by the corresponding letters over the F340/F380 trace in A. (C, D) The mean data of the amplitude of cell shortening (C) and Ca2+ transient (D) before and after application of PQ. Data are expressed as mean ± SD (n = 11). Cell shortening was normalized to resting cell length.
Fig 4.
(A) Families of current traces elicited by a series of 400-ms long depolarizing or hyperpolarizing pulses from a holding potential of −80 mV in the absence and presence of 3 and 10 μM PQ. (B, C) Averaged I–V relationship for Ito and IK1 peak currents (B) and Iss (C) observed in the absence, and presence of 1, 3, and 10 μM PQ. Peak Ito current was measured as the difference between the peak current and the steady-state current at the end of the pulse. Iss current was measured as the steady-state current at the end of the pulse. Each data point indicates mean ± SD from 5 myocytes. (D) Percent inhibition of the Ito integral by 1, 3, and 10 μM PQ calculated at different depolarizing potentials. Data points are mean ± SD (n = 5). (E) Original superimposed families of current traces generated by 400-ms depolarizing pulses to +40 mV from a holding potential of −80 mV in the absence or presence of increasing PQ concentrations. The arrow indicates the zero current density level. (F) Concentration–response curve for the effect of PQ on the integral of Ito at +40 mV. Data points are mean ± SD (n = 5). The continuous line was drawn according to the fitting of the Hill equation.
Fig 5.
Voltage dependence of steady-state Ito activation and inactivation in the absence and presence of 3 μM PQ.
Steady-state inactivation was examined with a double-pulse protocol: A conditioning 400 ms pulse to various potentials ranging from −80 to +10 mV was followed by a test depolarizing pulse to +60 mV (B, inset). The holding potential was −80 mV. The predrug superimposed current traces are shown in A. The inactivation curves for Ito were obtained by normalizing the current amplitudes (I) to the maximal value (Imax) and plotted as a function of the conditioning potentials before and after PQ (n = 5). The activation curves were obtained from the normalized conductance of Ito channels (Gto/Gto, max), which were calculated from the Ito amplitude in Fig 4B and plotted as a function of the depolarizing potentials (n = 5). The solid lines drawn through the data points were best fitted to the Boltzmann equation. (C, D) Effects of PQ on reactivation of Ito. The twin-pulse protocol consisted of two identical 200 ms depolarizing pulses to +60 mV from a holding potential of −80 mV (D, inset), and the prepulse–test pulse interval varied between 10 and 550 ms. An example of the recovery of Ito from inactivation in control conditions is shown in C. The normalized currents (fractional recovery) obtained in the absence and presence of 3 μM PQ were plotted as a function of the recovery time. The solid lines represent a single exponential fit to the data in the absence and presence of 3 μM PQ (n = 5), respectively.