Multiple effects of 4-aminopyridine on feline and rabbit sinoatrial node myocytes and multicellular preparations.
4-aminopyridine (4-AP) is commonly used to block the transient outward potassium current, I(to), in cardiac and noncardiac tissues. In the present work, we found that 4-AP inhibited the rapid component of the delayed rectifier potassium current, I(Kr), in rabbit-isolated sinoatrial node myocytes by 25% (1 mM) and 51% (5 mM) and inhibited the slow component of the delayed rectifier potassium current, I(Ks), in cat- isolated sinoatrial node myocytes by 39% (1 mM) and 62% (5 mM). In cat- and rabbit-isolated sinoatrial node myocytes, 4-AP activated muscarinic receptors in a voltage-dependent manner to increase the acetylcholine-activated potassium current, I(KACh). In multicellular preparations of the central region of the sinoatrial node from nonreserpinized rabbits, 4-AP produced an increase in action potential overshoot, frequency, and rate of diastolic depolarization. In the presence of the beta-adrenergic antagonist propranolol, 4-AP produced a marked increase in duration and a marked decrease in maximum diastolic potential and eventually, cessation of the spontaneous activity in preparations from the sinoatrial central region. In multicellular preparations from reserpinized rabbits, 4-AP produced similar effects to those observed in the presence of propranolol. We conclude that 4-AP inhibits multiple cardiac K(+) currents, including I(to), I(Kr), and I(Ks), and that these activities mask I(KACh) activation. In addition, in multicellular preparations, 4-AP produces neurotransmitter release from the autonomic nerve terminals. These multiple effects need to be considered when using 4-AP as a "specific" I(to) blocker.
Aréchiga-Figueroa
Iván A
IA
Unidad Carlos Méndez del Centro Universitario de Investigaciones Biomédicas de Universidad de Colima, Colima, Colima México.
Rodríguez-Martínez
Martin
M
Albarado
Alondra
A
Torres-Jácome
Julián
J
Sánchez-Chapula
José A
JA
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001514:Bee Venoms / Q000494:pharmacology; D002415:Cats; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology* / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D001514:Bee Venoms; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; C029738:tertiapin; D001285:Atropine; D015761:4-Aminopyridine