Figure 1.

Suppressant effect of EPA on the voltage-activated L-type Ca²⁺ current in adult rat ventricular myocytes. (A) Superimposed current density traces were elicited by 200-ms pulses with 10-mV increments from a potential of −50 mV to 50 mV. From a holding potential of −80 mV, brief depolarizations were applied to maintain a constant intracellular Ca²⁺ load. To elicit a test pulse, a slow ramp from −80 to −60 mV was applied, and the membrane potential was held at −60 mV for 50 ms before the test depolarization was applied. Current records under control conditions (open circles), 1.5 μM EPA (filled circles), and re-control (crosses) are shown (Upper) from a typical cell while averaged normalized current density-voltage relationships are shown (Lower) for control (n = 11), 1.5 μM EPA (n = 11) and washout (n = 5) are shown. The current density values were normalized to the maximum level observed under control conditions for each experiment. (B) Effects of EPA on the steady-state inactivation curve for I_Ca,L adult rat ventricular myocytes. Holding potential of −80 mV with prepulses to maintain constant SR Ca²⁺ load as in A. A slow depolarizing ramp was applied from −80 to −60 mV to inactivate I_Na. The membrane potential was immediately changed to the test potential for 1 s to produce a steady-state inactivation of I_Ca before stepping to 0 mV for 200 ms to assess I_Ca. (Left) Superimposed original Ca²⁺ current density records for cells exposed to no EPA (control, open circles) and for cells exposed to 10 μM EPA (closed circles). (Right) Normalized steady-state inactivation of peak I_Ca showing control (open circles) with fitting parameters of V_0.5 = −31.97 ± 1.1 mV and K = 5.2 ± 0.26 (n = 11), 10 μM EPA (filled circles) with fitting parameters of V_0.5 = −34.53 ± 1.1 mV and K = 5.11 ± 0.15 (n = 11) and washout (crosses) with fitting parameters of V_0.5 = −31.86 ± 0.9 mV and K = 4.9 ± 0.13 (n = 5). Control and EPA curves are significantly different (P < 0.05).