title: Block of NA+ and K+ currents in rat ventricular myocytes by quinacainol and quinidine.
abstract: 1. The electrophysiological actions of quinacainol were investigated on sodium (I(Na)), transient outward (i(to)) and sustained-outward plateau (iKsus) potassium currents in rat isolated cardiac myocytes using the whole-cell patch-clamp technique and compared with quinidine. 2. Quinacainol blocked sodium currents in a concentration-dependent manner and with a potency similar to that of quinidine (mean (+/-SEM) EC50 50+/-12 vs 95+/-25 micromol/L for quinidine and quinacainol, respectively). However, quinacainol had a considerably prolonged onset and recovery from block compared with quinidine. 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. 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(to) current amplitude, increased the rate of inactivation of i(to) and blocked iKsus. 5. These results indicate that quinacainol, a quinidine analogue, blocks sodium currents in cardiac myocytes with little effect on i(to) or iKsus potassium currents, which suggests that quinacainol may be exerting class 1c anti-arrhythmic actions.
authors.affiliation: Department of Pharmacology, Forest Research Institute, Jersey City, New Jersey, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Pugsley
authors.forename: Michael J A
authors.initials: MJ
authors.lastname: Walker
authors.forename: David A
authors.initials: DA
authors.lastname: Saint
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006352:Heart Ventricles / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D012996:Solutions
chemical_list: D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011804:Quinolines; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012996:Solutions; C037907:quinacainol; D011802:Quinidine