Apamin Does Not Inhibit Human Cardiac Na(+) Current, L-type Ca(2+) Current or Other Major K(+) Currents

BACKGROUND: Apamin is commonly used as a small-conductance Ca(2+)-activated K(+) (SK) current inhibitor. However, the specificity of apamin in cardiac tissues remains unclear. OBJECTIVE: To test the hypothesis that apamin does not inhibit any major cardiac ion currents. METHODS: We studied human embryonic kidney (HEK) 293 cells that expressed human voltage-gated Na(+), K(+) and Ca(2+) currents and isolated rabbit ventricular myocytes. Whole-cell patch clamp techniques were used to determine ionic current densities before and after apamin administration. RESULTS: Ca(2+) currents (CACNA1c+CACNB2b) were not affected by apamin (500 nM) (data are presented as median [25(th) percentile;75(th) percentile] (from –16 [–20;–10] to –17 [–19;–13] pA/pF, P = NS), but were reduced by nifedipine to –1.6 [–3.2;–1.3] pA/pF (p = 0.008). Na(+) currents (SCN5A) were not affected by apamin (from –261 [–282;–145] to –268 [–379;–132] pA/pF, P = NS), but were reduced by flecainide to –57 [–70;–47] pA/pF (p = 0.018). None of the major K(+) currents (I (Ks), I (Kr), I (K1) and I (to)) were inhibited by 500 nM of apamin (KCNQ1+KCNE1, from 28 [20]; [37] to 23 [18]; [32] pA/pF; KCNH2+KCNE2, from 28 [24]; [30] to 27 [24]; [29] pA/pF; KCNJ2, from –46 [–48;–40] to –46 [–51;–35] pA/pF; KCND3, from 608 [505;748] to 606 [454;684]). Apamin did not inhibit the I (Na) or I (CaL) in isolated rabbit ventricular myocytes (I (Na,) from –67 [–75;–59] to –68 [–71;–59] pA/pF; I (CaL), from –16 [–17;–14] to –14 [–15;–13] pA/pF, P = NS for both). CONCLUSIONS: Apamin does not inhibit human cardiac Na(+) currents, L-type Ca(2+) currents or other major K(+) currents. These findings indicate that apamin is a specific SK current inhibitor in hearts as well as in other organs.