Abstract
We have investigated the action of 9-amino-1, 2, 3, 4-tetrahydroacridine (THA) on the pacemaker current I f in rabbit sino-atrial node myocytes and in canine Purkinje fibres. THA at concentrations in the range 3–300 μM blocked I f in a voltage-independent manner, as revealed by measurements on the fully activated I/V relation for I f. The dose/response relationship of the I f maximal slope conductance (Gf) can be fitted by assuming a cooperative binding reaction where two THA molecules are required to block one I f 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 I f 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, I k, was also reduced by THA in sino-atrial node myocytes: at −40 mV the I k 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 I f at a lower concentration than other known I f-channel blockers [DiFrancesco (1982) J Physiol (Lond) 329:485-507], its action on the pacemaker current is not specific.
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DiFrancesco, D., Porciatti, F., Janigro, D. et al. 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. Pflügers Arch 417, 611–615 (1991). https://doi.org/10.1007/BF00372959
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DOI: https://doi.org/10.1007/BF00372959