Apamin does not inhibit human cardiac Na+ current, L-type Ca2+ current or other major K+ currents.

BACKGROUND

Apamin is commonly used as a small-conductance Ca2+-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 Ca2+ currents and isolated rabbit ventricular myocytes. Whole-cell patch clamp techniques were used to determine ionic current densities before and after apamin administration.

RESULTS

Ca2+ currents (CACNA1c+CACNB2b) were not affected by apamin (500 nM) (data are presented as median [25th percentile;75th 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 (IKs, IKr, IK1 and Ito) 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 INa or ICaL in isolated rabbit ventricular myocytes (INa, from -67 [-75;-59] to -68 [-71;-59] pA/pF; ICaL, 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 Ca2+ 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.