Effects of dronedarone on acetylcholine-activated current in rabbit SAN cells

Claudia Altomare, Andrea Barbuti, Carlo Viscomi, Mirko Baruscotti, Dario DiFrancesco

Research output: Contribution to journalArticle

Abstract

1. The effect of the antiarrhythmic drug dronedarone on the Acetylcholine-activated K + current (I(K(ACh))) was investigated in single cells isolated from sinoatrial node (SAN) tissue of rabbit hearts. 2. Externally perfused dronedarone (0.001-1 μM) caused a potent, voltage independent block of I(K(ACh)). Fitting of the dose response curve of I(K(ACh)) block yielded an IC 50 value of 63 nM, a value over one order of magnitude lower than those reported for dronedarone block of other cardiac currents. 3. I(K(ACh)) block was not due to an inhibitory action of dronedarone on the muscarinic M2 receptor activation, since the drug was effective on I(K(ACh)) constitutively activated by intracellular perfusion with GTP-γS. 4. External cell perfusion with dronedarone inhibited the activity of I(K(ACh)) channels recorded from cell-attached patches by reducing the channel open probability (from 0.56 to 0.11) without modification of the single-channel conductance. 5. These data suggest that dronedarone blocks I(K(ACh)) channels either by disrupting the G-protein-mediated activation or by a direct inhibitory interaction with the channel protein.

Original languageEnglish
Pages (from-to)1315-1320
Number of pages6
JournalBritish Journal of Pharmacology
Volume130
Issue number6
Publication statusPublished - 2000

Keywords

  • Amiodarone
  • Dronedarone
  • I(K(ACh))
  • Single channel
  • Sinoatrial node

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Altomare, C., Barbuti, A., Viscomi, C., Baruscotti, M., & DiFrancesco, D. (2000). Effects of dronedarone on acetylcholine-activated current in rabbit SAN cells. British Journal of Pharmacology, 130(6), 1315-1320.