Description:
<jats:title>SUMMARY</jats:title><jats:p>1. The electrophysiological actions of quinacainol were investigated on sodium (I<jats:sub>Na</jats:sub>), transient outward (i<jats:sub>to</jats:sub>) and sustained‐outward plateau (i<jats:sub>Ksus</jats:sub>) potassium currents in rat isolated cardiac myocytes using the whole‐cell patch‐clamp technique and compared with quinidine.</jats:p><jats:p>2. Quinacainol blocked sodium currents in a concentration‐dependent manner and with a potency similar to that of quinidine (mean (±SEM) EC<jats:sub>50</jats:sub> 50 ± 12 <jats:italic>vs</jats:italic> 95 ± 25 µmol/L for quinidine and quinacainol, respectively). However, quinacainol had a considerably prolonged onset and recovery from block compared with quinidine.</jats:p><jats:p>3. Neither quinacainol nor quinidine significantly changed the steady state voltage dependence of activation of sodium currents. Quinidine produced a hyperpolarizing shift in the voltage dependence for sodium current inactivation, but no such shift was observed with quinacainol at doses that produced a substantial current block.</jats:p><jats:p>4. Although quinacainol did not effectively block voltage‐dependent potassium currents, even at concentrations as high as 1.5 mmol/L, quinidine, at a half‐maximal sodium channel‐blocking concentration, reduced peak i<jats:sub>to</jats:sub> current amplitude, increased the rate of inactivation of i<jats:sub>to</jats:sub> and blocked i<jats:sub>Ksus</jats:sub>.</jats:p><jats:p>5. These results indicate that quinacainol, a quinidine analogue, blocks sodium currents in cardiac myocytes with little effect on i<jats:sub>to</jats:sub> or i<jats:sub>Ksus</jats:sub> potassium currents, which suggests that quinacainol may be exerting class 1c anti‐arrhythmic actions.</jats:p>