Nicotine abuse is associated with variety of diseases including arrhythmias, most often atrial fibrillation (AF). Altered inward rectifier potassium currents including acetylcholine-sensitive current I K(Ach) are known to be related to AF pathogenesis. Since relevant data are missing, we aimed to investigate I K(Ach) changes at clinically relevant concentrations of nicotine. Experiments were performed by the whole cell patch clamp technique at 23 ± 1 °C on isolated rat atrial myocytes. Nicotine was applied at following concentrations: 4, 40 and 400 nM; ethanol at 20 mM (∼0.09%). Nicotine at 40 and 400 nM significantly activated constitutively active component of I K(Ach) with the maximum effect at 40 nM (an increase by ∼100%); similar effect was observed at -110 and -50 mV. Changes at 4 nM nicotine were negligible on average. Coapplication of 40 nM nicotine and 20 mM ethanol (which is also known to activate this current) did not show cumulative effect. In the case of acetylcholine-induced component of I K(Ach), a dual effect of nicotine and its correlation with the current magnitude in control were apparent: the current was increased by nicotine in the cells showing small current in control and vice versa. The effect of 40 and 400 nM nicotine on acetylcholine-induced component of I K(Ach) was significantly different at -110 and -50 mV. We conclude that nicotine at clinically relevant concentrations significantly increased constitutively active component of I K(Ach) and showed a dual effect on its acetylcholine-induced component, similarly as ethanol. Synchronous application of nicotine and ethanol did not cause additive effect.
- Klíčová slova
- Acetylcholine-sensitive, Dual effect, Inward rectifier, Nicotine,
- MeSH
- acetylcholin farmakologie MeSH
- časové faktory MeSH
- dovnitř usměrňující draslíkové kanály spřažené s G proteiny agonisté účinky léků MeSH
- ethanol toxicita MeSH
- hodnocení rizik MeSH
- kardiomyocyty účinky léků metabolismus MeSH
- membránové potenciály MeSH
- nikotin toxicita MeSH
- potkani Wistar MeSH
- srdeční arytmie chemicky indukované metabolismus MeSH
- srdeční síně účinky léků metabolismus MeSH
- techniky in vitro MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- acetylcholin MeSH
- dovnitř usměrňující draslíkové kanály spřažené s G proteiny MeSH
- ethanol MeSH
- nikotin MeSH