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 language | English (US) |
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Pages (from-to) | 611-615 |
Number of pages | 5 |
Journal | Pflügers Archiv European Journal of Physiology |
Volume | 417 |
Issue number | 6 |
DOIs | |
State | Published - 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)