Figure 9.

Reduction of voltage-gated Na⁺ current by D1-type dopamine receptor activation. Ruptured-patch configuration at 34 °C; voltage-clamp mode with no leak subtraction. Currents activated in a single cell by 4-msec depolarizations (A) and 1-sec hyperpolarizations (B). Holding potential was −72 mV. Test potentials were −57 mV and −47 mV to activate voltage-gated Na⁺ current (A, grey and black traces, respectively) and −77, −92, and −107 mV to activate I_h (B). Stimulus timing and polarity shown by steps above current traces. Triangles at left show zero-current level for all traces in each row. As labeled above current traces in A, solution superfused over cell was changed from control (A₁, B₁) to 3 mM Cs⁺ (A₂, B₂), 6 μM dopamine and 3 mM Cs⁺ (A₃, B₃), 6 μM dopamine, 3 mM Cs⁺, and 5 μM SCH-23390 (A₄, B₄), 6 μM dopamine, 3 mM Cs⁺, 5 μM SCH-23390, and 1 μM TTX (A₅, B₅), and control (A₆, B₆). Peak amplitude of depolarization-activated Na⁺ current at −47 mV in dopamine (A₃, black trace) is 10% smaller than in control (A₁). This reduction was reversed by SCH-23390 (A₄). The depolarization-activated current was blocked by 1 μM TTX (A₅), leaving small uncompensated capacitive inward and no outward current. This TTX block, and the block of I_h by Cs⁺, were reversed by washing with control solution (A₆, B₆). The activation threshold and increase in Na⁺ current by the increment in step depolarizations, and the increase in I_h by the increment in step hyperpolarizations, were similar at the beginning and end of this recording. C: Na⁺ current amplitudes of all cells tested (n=6) as in A, B. Na⁺ current peak amplitude normalized to value in Cs⁺ (left) after reduction by dopamine (middle) and recovery in SCH-23390 (right) while I_h was suppressed. The mean in Cs⁺ differed significantly from that in Cs⁺ plus dopamine (P<0.0005, paired t-test).