Block of the cardiac pacemaker current (If) in the rabbit sino-atrial node and in canine Purkinje fibres by 9-amino-1,2,3,4-tetrahydroacridine

D. DiFrancesco*, F. Porciatti, D. Janigro, G. Maccaferri, M. Mangoni, T. Tritella, F. Chang, I. S. Cohen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

We have investigated the action of 9-amino-1, 2, 3, 4-tetrahydroacridine (THA) on the pacemaker current If in rabbit sino-atrial node myocytes and in canine Purkinje fibres. THA at concentrations in the range 3-300 μM blocked If in a voltage-independent manner, as revealed by measurements on the fully activated I/V relation for If. The dose/response relationship of the If maximal slope conductance (Gf) can be fitted by assuming a cooperative binding reaction where two THA molecules are required to block one If channel. Half-maximal block occurred at 18.2 μM in the sino-atrial node and 36.6 μM in Purkinje fibres. THA also affected the If kinetic properties. This was examined in the sino-atrial node where the current activation curve was shifted in the negative direction on the voltage axis (-21 mV at 30 μM THA). The delayed rectifier current, Ik, was also reduced by THA in sino-atrial node myocytes: at -40 mV the Ik fully activated value was decreased to 37% of its control value by 30 μM THA, with only a minor modification of the position of the activation curve at the same potential. Thus, although THA blocks If at a lower concentration than other known If-channel blockers [DiFrancesco (1982) J Physiol (Lond) 329:485-507], its action on the pacemaker current is not specific.

Original languageEnglish (US)
Pages (from-to)611-615
Number of pages5
JournalPflügers Archiv European Journal of Physiology
Volume417
Issue number6
DOIs
StatePublished - Feb 1991

Keywords

  • 9-amino-1, 2, 3, 4-tetrahydroacridine
  • Block
  • Pacemaker current (I)
  • Purkinje fibre
  • sino-atrial node

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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