Fig. 5.
Sodium channel inhibition by σ-receptor ligands in cardiac myocytes. INa was evoked by steps from −80 mV to −10 mV in neonatal cardiac myocytes from wild-type (A) and σ1-receptor knockout (B) mice in the absence (control, black), presence (drug, red), and after washout (recovery, blue) of 100 μM SKF-10047, (+)-pentazocine, haloperidol, and DTG. Insets: normalization revealed that inhibition occurred without a change in channel kinetics [pentazocine (A) and DTG (B)]. Note that SKF-10047 and (+)-pentazocine, two σ1-receptor-specific ligands, inhibit INa by ∼50% in wild-type mice (A) and 20% or less in knockout (B) mice. By contrast, haloperidol and DTG, two nonspecific σ-receptor ligands, inhibited INa by ∼90 ± 3% in both wild-type and knockout mice (see Fig. 6).